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Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

Studies on fertility, respectively multi-generation studies are not available for aniline and appear scientifically not necessary. Based on the available information on organs of the male and female reproductive system from three chronic studies there is no suspicion for effects on fertility it is proposed not to perform an additional study regarding effects on fertility.

Data on organ weights for testes with epididymides and for ovaries as well as information on gross pathology and on histopathology of the high-dose treated animals for reproductive organs of both sexes can be derived from a 104-week chronic toxicity feeding study with Fischer 344 albino rats (CIIT, 1982). In this study groups of 130 animals/sex had been treated with aniline hydrochloride in the diet at doses according to approximately 7, 22, and 72 mg aniline/kg bw/day. At 26 and 52 weeks, ten rats of each sex in each group, and at week 78, twenty rats of each sex in each group were sacrificed intermittently.The remaining 90 animals were terminated at the end of the study. No apparent treatment-related effects were observed for the male reproductive system in comparison to the controls in terms of testes weight and testes histopathology at either time interval or at final termination. In the females absolute and relative ovary weight in treated animals were slightly higher but not statistically significantly different from that of the control groups after 26, 52 and 78 weeks on diet. At termination after 104 weeks absolute and relative ovary weight was statistically significantly lower in the high-dose group (0.095 g, respectively 0.36%) than in controls (0.190 g, respectively 0.71%). An increased incidence of uterine endometrial polyps was recorded during histopathological evaluations in aniline treated dams after 78 weeks only, with six high-dose, three mid-dose and two low-dose females afflicted, while only one case was observed in the control group. No such effect was recorded at the evaluation after 26 and 52 weeks nor at the end of the study (104 weeks). Since uterine endometrial polyps are a common observation for this rat strain, the isolated observation at 78 weeks of exposure only of a treatment-related increase in the incidence of uterine endometrial polyps is considered an incidental finding. From the overall evaluations of this study a clear substance-related induction of uterine endometrial polyps could not be established (CIIT, 1982; ECB, 2004).

Furthermore aniline hydrochloride had been applied to B6C3F1mice and F344 rats in a 103-week feeding study (NCI, 1978). Groups of 50 mice each received a low-dose level of 0.6% in diet (body dose of approximately 737 mg aniline/kg bw/day) and a high-dose level of 1.2% in diet (body dose of approximately 1510 mg aniline/kg bw/day). Groups of 50 rats each received a low-dose level of 0.3% in diet (body dose: approximately 174.4 mg aniline/kg bw/day) and a high-dose level of 0.6% in diet (body dose: approximately 350.5 mg aniline/kg bw/day). In this study organs of the reproductive system had been monitored histopathologically for neoplastic as well as for non neoplastic lesions. In mice no treatment-related effects in any of the organs of the reproductive system of either males or females were reported for doses up to and including approximately 1510 mg aniline/kg bw/day. Also, for male rats no effects in any of the organs of the reproductive system attributable to treatment were reported with doses up to and including approximately 350.5 mg aniline/kg bw/day. In female rats after 103 weeks increased incidences of uterine endometrial polyps were reported with 15/48 (31%) animals of the low-dose group and with 7/50 (14%) animals of the high-dose group afflicted in comparison to 2/24 (8%) animals of the control group. The occurrence of endometrial polyps in untreated as well as in treated animals of this rat strain was also mentioned in the above cited CIIT study (CIIT, 1982).

Effects on developmental toxicity

Additional information

For the assessment of developmental toxicity an appropriate study in rats with oral doses of approximately 7, 22 and 72 mg aniline/kg/day from gestation day (GD) 7 to GD 20 or GD 7 through parturition is available (Price et al., 1985). Furthermore, dams were kept until post parturiton day (PD) 30 and pubs until PD 60 for examination of possible developmental toxicity.

At termination on GD 20 dams of all dose groups exhibited characteristic signs of aniline toxicity, i.e., methemoglobinemia, increased relative spleen weight, decreased red blood cell (RBC) count, and hematological changes indicative of increased hematopoietic activity. High-dose dams exhibited mild methemoglobinemia, increased relative spleen weight, and increased RBC size at termination on post parturition day 30.

At termination on GD 20, fetuses from aniline treated dams exhibited increased relative liver weight and enhanced hematopoietic activity, but no evidence of an embryolethal or teratogenic effect was observed. Postnatal signs of toxicity in litters from aniline treated dams (decreased body weight, elevated relative liver weight, and elevated relative spleen weight) were transient, and no evidence of treatment related toxicity was observed in pups on PD 60.

Thus, no toxicity other than the expected hematotoxicty and related effects were observed in both, dams and pubs after treatment with aniline.

Justification for classification or non-classification

Based on the available information on aniline induced toxicity on the male and female reproductive tract and the available appropriate study on developmental toxicity in rats classification regarding effects on fertility and development is not warranted according to the criteria outline in Annex VI to 67/548/EEC as well as Annex I to the CLP regulation (EC) 1272/2008. Non-classification for toxicity to reproduction is in accordance with the entries for harmonized classification and labelling in Annex VI to the CLP regulation.

Additional information