Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
500 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

To address toxicological endpoints as part of the REACH registration of Lemonile (Target Substance) it is proposed to read-across to Citronellyl Nitrile (Source Substance). The use of read-across works within the spirit of REACH and the stated aim of the legislation to reduce animal testing where possible. The Target Substance and Source Substance have been characterised in using the categories and databases present in the OECD [Q]SAR Toolbox. From the profiling, it can be seen that the two substances share structural similarities and also ‘mechanistic action’ similarities which are both general and endpoint specific. Therefore read across is justified.

See Section 13, document, Read across justification_Citronellyl nitrile.

1 -Generation reproduction study (OECD 415)

Based on the results of the OECD 415 study, the no-observable-adverse-effect-level (NOAEL) for toxicity of citronellyl nitrile is 200 mg/kg/day. Increased incidences of excess salivation and/or ungroomed coat occurred in P generation male and/or female rats in the 500 mg/kg/day dosage group. However, these clinical signs were not considered an adverse effect of citronellyl nitrile. At 500 mg/kg/day, sporadic reductions in body weight gains occurred in male rats prior to cohabitation, followed by persistent reductions in weight gain through the end of the study. Non-reproductive organ weights were affected in both sexes at the end of the dosage period, as well as terminal body weights. Increased brain and spleen weights occurred in male rats treated with 500 mg/kg/day citronellyl nitrile, while increased liver and kidney weights occurred in both sexes in this same dosage group. The toxicological significance of the increased organ weights was unable to be determined because there were no microscopic findings that could be correlated with the changes in organ weights.

The reproductive NOAEL in the P generation rats and the NOAEL for viability and growth of the F1 generation offspring is greater than 500 mg/kg/day. There were no apparent effects on estrous cycling, mating and fertility, reproductive organ weights ornatural delivery parameters in the P generation and growth and development (including anogenital distance, nipple eruption or sexual maturation) in the F1 generation rats at the highest dosage level tested (500 mg/kg/day).


Short description of key information:
OECD 415 (Citronellyl nitrile): NOAEL for toxicity is 200 mg/kg/day.
The reproductive NOAEL in the P generation rats and the NOAEL for viability and growth of the F1 generation offspring is greater than 500 mg/kg/day.

Justification for selection of Effect on fertility via oral route:
The Target Substance and Source Substance have been characterised in using the categories and databases present in the OECD [Q]SAR Toolbox. From the profiling, it can be seen that the two substances share structural similarities and also ‘mechanistic action’ similarities which are both general and endpoint specific. Therefore read across is justified.

Effects on developmental toxicity

Description of key information
No data available. 
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Pre-natal development

During the OECD 415 study there was no evidence in the females or F1generation rats that indicated a concern with pre-natal development. Furthermore, systemic exposure is considered to be very low via skin (most likely route of exposure) hence,

it is considered unjustified and unnecessary to conduct a pre-natal developmental study on this substance.

Justification for selection of Effect on developmental toxicity: via oral route:
Pre-natal development
During the OECD 415 study there was no evidence in the females or F1 generation rats that indicated a concern with pre-natal development. Furthermore, systemic exposure is considered to be very low via skin (most likely route of exposure) hence,it is considered unjustified and unnecessary to conduct a pre-natal developmental study on this substance.

Justification for classification or non-classification