| TSCA Test Submissions | Acute dermal toxicity was evaluated in groups of 4 male albino New Zealand strain rabbits receiving single occluded applications of undiluted E-caprolactam at dose levels of 0.5, 1.0 and 2.0 gm/kg of body weight. The test material was held in contact with the intact skin for a 24 hour period. Mortality was observed in 1 animal in the 0.5 gm/kg dose group and in all animals in the 2.0 gm/kg dose group (period of observation not reported)the LD50 was calculated to be 1.41 gm/kg of body weight. Clinical observation were not reported. Gross necropsy revealed mottled livers, congested and hemorrhagic lungs and congested kidneys.Caprolactam (CAS # 105-60-2) was evaluated for acute inhalation toxicity in SPF1-Wistar/Chbb rats (10/sex/group) administered single nose-only exposures to the aerosol (MMAD 50% = 2.69 um86.6% capable of alveolar exposure) in air at mean analytical concentrations of 0, 5.25, 8.35, and 10.12 mg/l for 4 hours. During exposures, the animals exhibited eyelid closure, shallow to spasmodic respiration, and mild to marked defense reactionssteppage gait, bloody nasal exudate, spasmodic respiration, bloody lacrimation, squatting, bristling fur, and severe tremor were noted during 14-day post-exposure recovery. No change in bodyweights or bodyweight gains after exposures could be attributed to substance exposure. Mortality was dose-related, occurred before Day 2 following exposures, and was consistent with LD50's of 9.6 and 7.08 mg/l (p < 0.05 based on a probit analysis of D.J. Finney), respectively, for male and female rats. Among study lethalities, gross pathology on necropsy included general circulatory congestion, elevated hyperemia of the lung, and moderate to severe fatty degeneration of the liver. Histologic evaluation revealed fine-droplet fatty degeneration of peripheral acini in the liver and ischemic tubular nephrosis of the renal cortex in a solitary lethality of a 10.12 mg/l exposure.The effect of subchronic dietary treatments on renal function was evaluated in groups of 6 male and 6 female Fischer 344, Sprague-Dawley and Wistar strain rats administered caprolactam at dietary levels of 0. 0.01, 0.05, 0.1, and 0.5%, available ad libitum, for 90 days. Mortality was observed in one Sprague-Dawley male from the 0.01% feeding level. Clinical observations revealed no treatment-related effects. Body weight were significantly lower (p <= 0.05) than controls in: Fischer 344 females at the 0.50% levelin Sprague-Dawley males at the 0.1% and 0.5% levelsin Sprague-Dawley females at the 0.01%, 0.05% and 0.50% levelsin Wistar males at 0.05% and 0.50%and in Wistar females at 0.50%. Serum chemistry analysis revealed significant increases (p <= 0.05) in BUN, serum chloride levels and decreases in BUN, serum creatine levels, serum chloride levels, serum sodium levels, and serum hematocrit levelsthese results, however, appear to be random and not related to the test material. Urinalysis data revealed dose-related increases in urine volume in Fischer 344 males and females at the 3 highest doses. Dose related increases in the kidney/body weight ratio were observed in Sprague-Dawley males at 0.10 and 0.50% and in Wistar males at 0.50%. Gross necropsy revealed no compound-related incipient nephrosis, chronic inflammation, cytomegalic and chromophobic epithelial cells, protenaceous deposits, increased cytoplasmic vacuolization int eh tubules, increased hyalin droplets, and tubular epithelial hyperplasia and basophilia. In a similar study also evaluating the effects of caprolactam, the only compound-related effect was the altering renal function (fractional reabsorption of water) at the highest dose level (0.50%).Caprolactam (CAS # 105-60-2) was evaluated for subchronic oral toxicity specific to the kidney in groups (100/sex/strain) of Fischer 344, Sprague-Dawley, and Wistar rats randomized to nominal dietary exposures (ad libitum) of 0, 0.01, 0.05, 0.10, and 0.50% for a minimum 84 of 90 consecutive days. Dietary exposures were continued as rats of each strain (2 x 6, 2 x 8 and 2 x 6/sex/dose group) participated in Phases I and II of 3 distinct analyses of previously documented or implied renal toxicity: Phase 1 employed non-invasive techniques to establish the locale of renal toxicity, dose-response correlation, and sex and/or strain specificity by (Part A) measurement of biological markers of degenerative effects on the renal early proximal tubule (PT) and PT reabsorptive processes and (Parts B & C) determination of relative sensitivity and expression of toxicity in stressed (dehydrated or extracellular volume expansion) kidneys. Phase II used invasive procedures on anesthetized animals to (Part A) monitor proteinaceous material in Bowman space and/or the proximal tubule, and (Part B) directly measure glomerular filtration, urine clearance or reabsorption of free water and electrolytes, and blood and urine osmolality. Recovery from (Part A) any nephrotoxic effects (functional and/or histological) and, (Part B, per protocol amendment) specifically those effects documented in Phase 1 was examined in Phase III animals allowed 90-day recovery following cessation of 90 days' dietary exposure. Only all-strain lethalities and those strains demonstrating histological renal toxicity in Phase 1 high dose groups were terminated by pathology in Phase II (for light microscopy evaluation of changes in function and structure per protocol amendment) and Phase III (for evidence of recovery from toxic effects). Results of Phase I revealed functional nephrotoxicity in the stressed kidney only, including inhibited natriuresis upon volume expansion and diminished urine concentrating capacity during water deprivation, suggesting a distal tubule target of toxic action. Treated rats showed no gross pathology, but had increased kidney weights and increased incidence of hyalin droplets within renal tubules, more pronounced in males than females, and in Fischer 344 and Sprague-Dawley than in Wistar rats. Additionally, colloidal iron staining of glomeruli did not correlate with either level of exposure or with occurrence of tubular eosinophilic hyalin droplets. In Phase II, kidney weights were also increased and only fractional reabsorption of water in Fischer 344 or Sprague-Dawley high dose rats was altered, again supporting a distal tubule site of nephrotoxic effects in these strains. Based on urine concentrating capacity, the function of kidneys is fully reclaimed during 90-day recovery, which was verified on histological assessment concluding Phase III of study.For more TSCA Test Submissions (Complete) data for CAPROLACTAM (12 total), please visit the HSDB record page. |
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