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Key value for chemical safety assessment

Effects on fertility

Additional information

In the available combined repeat dose and reproductive/developmental toxicity screening test performed with a structural analogue substance, Trimethylamine (CAS No. 75-50-3), the substance was administered orally to male and female Sprague-Dawley rats (13 animals/sex/dose group). The exposure time was 42 days, one dose daily. The dose groups were 0, 8, 40, and 200 mg/kg/day, respectively. Two males and one female died in the 200 mg/kg group. Stridor and temporary salivation were observed in males and females of the 200 mg/kg group. Body weight tended to decrease and food consumption to decrease in males of the 200 mg/kg group. There were no adverse effects on reproductive organs. No alteration was observed for body weight or food consumption in females. The compound exerted no adverse effects on the estrous cycle, copulation and fertility, maintenance of pregnancy, parturition and lactation, as well as number of pups, delivery index, duration of pregnancy, number of corpora lutea and the implant rate at any dose level. The compound did not demonstrate any adverse effects on birth index, number of live pups, viability, sex ratio, body weight and morphological appearance of pups. The no observed effect dose level (NOEL) for reproductive and developmental toxicity is considered to be 200 mg/kg/day in males and females, and 200 mg/kg/day in pups, respectively.


Short description of key information:
No data available concerning reproduction toxicity for Diethylamine CAS 109-89-7.
Read-across Dibutylamin CAS No. 111-92-2 and Trimethylamin CAS 75-50-3 is proposed. Studies on teratogenicity are availabel for both structural analogues.Therefore, a repro screen is not required for Diethylamin CAS No. 109-89-7.
No data are available for Dibutylamin (DNBA) CAS No. 111-92-2 for the effects on fertility. However, in a combined repeat dose and reproductive/developmental toxicity screening test performed with a structural analogue substance, Trimethylamine (CAS No. 75-50-3), the no observed effect dose level (NOEL) for reproductive and developmental toxicity are considered to be 200 mg/kg/day in males and females, and 200 mg/kg/day in pups, respectively.

Effects on developmental toxicity

Description of key information
No data available concerning reproduction toxicity for Diethylamine CAS 109-89-7.
Read-across to Dimethylamin CAS No. 124-40-3 and Dibutylamin CAS No. 111-92-2 is sproposed. Studies on teratogenicity are availabel for both structural analogues.Therefore, a repro screen is not required for Diethylamin CAS No. 109-89-7.
No data are available for Dibutylamin CAS No. 111-92-2 for the effects on developmental toxicity/teratogenicity. Information can be derived from data for the Dibutylamin-Hydrochloride salt, where a Developmental Toxicity study (OECD 414) has been performed.
Additionally, to corroborate the read-across among the structural related Alkylamines – additional information can be derived from a study performed with the structural analogue substance, tri-n-Butylamine (CAS No. 102-82-9), the LOAEL for maternal toxicity was 135 mg/kg bw/day and the NOAEL 45 mg/kg bw/day. The NOAEL for developmental toxicity was 135 mg/kg bw/day, the highest dose tested. Moreover, data on an OECD 414 are also available for Dimethylamine (CAS No. 124-40-3).
Additional information

No data available concerning reproduction toxicity for Diethylamine CAS 109-89-7. Read across is proposed to the following substances: Dibutylamine CAS No. 111-92-2, Dimethylamin CAS No. 124 -40 -3 and Tri-n-Butylamin CAS 102 -89 -9 for the effects on developmental toxicity/teratogenicity.

Information can be derived from data for the Dibutylamine-Hydrochloride salt, where a Developmental Toxicity study (OECD 414) has been performed (ACC, 2010).

In the available developmental toxicity study, the oral administration of Dibutylamine hydrochloride to pregnant Wistar rats from implantation to one day prior to the expected day of parturition (GD 6-19) elicited maternal toxicity, such as clinical pathological effects at dose levels of 50 mg/kg bw/d and above, as well as additional clinical findings and a temporarily reduced body weight gain at a dose level of 150 mg/kg bw/d. In conclusion, the no observed adverse effect level (NOAEL) for maternal toxicity is 15 mg/kg bw/d. The no observed adverse effect level (NOAEL) for prenatal developmental toxicity is 150 mg/kg bw/d, the highest tested dose.

 

In the availabledevelopmental toxicity study (OECD 414) (Hoechst, )for the structural analogue tri-n-Butylamine CAS 102-82-9) pregnant Sprague-Dawley rats (20 per group) were orally treated with the substance by gavage on gestation days 6 -15 with doses of 15, 45 and 135 mg/kg/day. Three dams died prematurely on days 7 and 8. The other animals of this group showed transient reductions in food consumption and body weight gain. There were no embryo- or fetotoxic effects except a slight and dose-related increase in fetal body weight gain, which was significant at the highest dose. The treatment did not produce malformations (Hoechst/LPT, 1991). The LOAEL for maternal toxicity was 135 mg/kg bw/day, the NOAEL 45 mg/kg bw/day. The NOAEL for developmental toxicity was 135 mg/kg bw/day, the highest dose tested.

In another availabledevelopmental toxicity study (OECD 414) (ACC, 2009) for the Hydrochloride salt of the structural analogue Dimethylamine (CAS No. 124-40-3)

Dimethylamine hydrochloride was administered to pregnant Wistar rats daily by gavage from implantation (GD 6) to one day prior to the expected day of parturition (GD 19). The test substance did not cause any mortality. Test substance-related relevant clinical effects were only seen in the high-dose dams (1000 mg/kg bw/d), i.e. salivation after treatment and decreased food consumption, although the latter did not affect body weight, body weight gain, net body weight gain and uterus weight. At necropsy, no test substance related findings were noted in any of the dams. The temporary salivation was likely to be induced by the taste of the test substance or by local irritation of the upper digestive tract. It was not considered to be a sign of systemic toxicity. No differences of toxicological relevance between the control and the dose groups were determined for reproductive parameters such as conception rate, mean number of corpora lutea, mean number of implantations, pre- and postimplantation losses, live fetuses and fetal sex ratio. In summary, there was no evidence of an adverse effect of Dimethylamine hydrochloride on fetal morphology at any dose level tested.

Justification for classification or non-classification

Diethylamin CAS No. 109 -89 -7 is not warranted for classification and labelling according to Directive 67/548/EEC Annex I and

according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

No effects were observed inthe underlying studies and in close strutural analogues.