Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

In a three-generation study F344 rats were continuously fed with caprolactam (CAP) at dose levels of ca. 100, 500, 1000 mg/kg bw throughout three successive generations (Serota et al., 1981). Following the 10 weeks premating exposure periods, no treatment-related clinical signs of toxicity, changes in reproductive performance or gross-pathological findings were noted within the parental generations. Compound-related findings were mainly related to body weight loss (signifigant in the high-dose group only). Histopathologic findings noted in the high-dose P1 animals consisted of a slight increase in the severity of spontaneous nephropathies, occasionally accompanied by granular casts in 3 of 10 male animals. Based on these findings, the NOAEL for the parental P1-P3 generations was identified as 500 mg/kg bw.

Pregnancy and fertility indices were comparable between treated and control groups for each filial generation and no dose-related trends were apparent, thus the NOAEL for fertility was 1000 mg/kg bw.

The offspring data revealed no treatment-related effects with respect to gross appearance, gross pathology, survival, number of pups, and percentage of male pups or kidney weight. The only effect observed in offspring were lower mean body weights in male and female pups at the two highest dose levels in all filial generations, the NOAEL of F1-F3 offspring was 1000 ppm (100 mg/kg bw). Summarized no adverse effect on reproductive organs or function were found in this 3-generation study with rats.

These findings were supported by the 103-month Combined Chronic Toxicity / Carcinogenicity Study with Fischer rats (NTP 1982). No effects on reproductive organs (testes weights as well as information on gross and microscopic pathology for testes, prostate, ovaries, and uteri) were observed at the highest dose tested (375 mg/kg bw/day).

Effects on developmental toxicity

Additional information

In a Developmental toxicity study performed accorsing to the current OECD guideline 414, 20 F344 rats/group were gavaged with dose levels of 100, 500 and 1000 mg/kg/d bw on days 6-15 of gestation. The maternal survival rate was statistically lower in the high-dose group when compared with the control. Nine high-doses females were found dead during the treatment phase of this study. Clinical observations such as urine stains, rough hair coat, red discharge from the vagina, bloody crust on eyes, mouth and nose, and thin and/or hunched appearance were observed in dose dependent manner in all treated groups.

The mean body weight values of the high dose group were significantly (p<0.05) lower than in controls on days 15 (10%) and 20 (11%) of gestation. Furthermore, the mean body weight changes of the mid- and high-dose groups for the days 6-11 and 6-15 were significantly (p<0.05) lower than the control values at these intervals. These effects on body weights were accompanied by significantly lower values of mean food consumption in the mid- and high-dose groups. In these maternally toxic doses, a slight reduction in fetal body weight was observed. The mean number of corpora lutea and implantations per group were not affected by treatment, but the mean implantation efficiencies were slightly reduced in the high-dose group. No treatment-related visceral or skeletal anomalies were observed.

Based on these results in rats, the NOAEL for maternal toxicity was identified as 100 mg/kg bw/d, for embryotoxicity as 500 mg/kg bw/d and for teratogenicity as 1000 mg/kg bw/d.


In an analogous developmental toxicity study (Bio-Research, 1983) with New Zealand White Rabbits, 25 animals/group were gavaged with dose levels of 50, 150 and 250 mg/kg bw on days 6-28 of gestation. In the high dose group 4 rabbits died during the treatment period. Also exclusively in the high dose group, adverse clinical findings were observed. The absolute weight gain between day 6 and 29 was decreased in the high dose group, whereas the corrected body weight gain (body weight gain day 6-29 minus weight of gravid uterus) was significantly decreased in mid dose animals.

Fetotoxicity was evidenced by lower fetal weights at the mid and high dose groups, and an increased incidence of thirteenth ribs was observed in the high dose group. Neither embryotoxicity nor teratogenicity occurred. Based on these findings in rabbits, the NOAEL for maternal toxicity and fetotoxicity was identified as 150 and 50 mg/kg bw, respectively. No teratogenicty was observed with the highest dose tested (NOAELtera 250 mg/kg bw/day).


In a BASF study (1978), no signs of maternal toxicity and fetotoxicity were observed in rats after dosing 166 mg CAP/kg bw by oral-gavage. Thus, the NOAEL for maternal, fetal and developmental toxicity was above 166 mg/kg bw/d. 


Combining all data, no teratogenic effects from the oral application of CAP were observed in rats or rabbits. Fetotoxic effects were only observed in rats and rabbits at doses that also produced maternal toxicity.

Justification for classification or non-classification

No indications of reproductive toxicity were identified in a 3 -gen study in rats and no developmental toxicity was identified in developmental toxicity studies in ras and rabbits. Therefore no classification for toxicity to reproduction is warranted.