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Key value for chemical safety assessment

Effects on fertility

Additional information

In the key study, i.e. a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test according to OECD TG 422 and GLP, nerolidol was administered via the diet to Wistar rats at 0, 1500, 4000, 12000 ppm for 37 days (males) and 58 days (females), (BASF 96R0466/09052).

General systemic toxicity was noted in the parental males at 12000 ppm and in the parental females at 12000 and 4000 ppm. Salient findings were distinct decreases in food consumption and body weights/ body weight gain (which were most severe in females during gestation and lactation) as well as clinical pathological findings. Pathology revealed the liver to be the target organ of toxicity, showing increased weights in both sexes and central hepatocellular hypertrophy and central fatty change in females.

Nerolidol showed no adverse effects on fertility of the parental animals of both genders at 1500, 4000 and 12000 ppm. Almost all of the parental animals proved to be fertile. The occurence of one infertile pair each in test groups 1500 ppm and 12000 ppm do not suggest any treatment relation. Furthermore, gross and histopathological examinations of the respective animals of both genders did not reveal test substance-induced findings, which may have accounted for the observed infertility.

Nerolidol caused also no impairments of the reproductive performance. Mating behaviour, conception, gestation, parturition, as well as sexual organ weights and gross and histopathological findings of these organs were not influenced.

Developmental toxicity, i.e. slight reduction of offspring body weights/body weight gain exclusively at the top dose level of 12000 ppm, beeing secondary to maternal toxicity has been observed (see section “Developmental toxicity/ Teratogenicity”).

 

Taken together, the NOAEL for general toxicity in parental animals has been set to 4000 ppm (corresponding to about 270 mg/kg bw/d.) for males and 1500 ppm (corresponding to about 105, 120 or 193 mg/kg bw/d) for non-pregnant, pregnant or lactating females, respectively.

A NOAEL >= 12000 ppm has been set for fertility and reproductive performance, corresponding to about 755 mg/kg bw/d in males and 705, 824 or 1194 mg/kg bw/d in non-pregnant, pregnant or lactating females, respectively.

For developmental toxicity a NOAEL has been set at 4000 ppm, corresponding to about 270 mg/kg bw/d in males and 279, 340 or 468 mg/kg bw/d in non-pregnant, pregnant or lactating females, respectively.


Short description of key information:
Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (according to OECD TG 422 and GLP) (BASF 96R0466/09052):
NOAEL general toxicity males = 4000 ppm
NOAEL general toxicity females = 1500 ppm
NOAEL fertility/reproductive performance >= 12000 ppm

Effects on developmental toxicity

Description of key information
Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (according to OECD TG 422 and GLP) (BASF 96R0466/09052): 
NOAEL general toxicity males = 4000 ppm
NOAEL general toxicity females = 1500 ppm
NOAEL developmental toxicity = 4000 ppm
Additional information

In the key study, i.e. a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test according to OECD TG 422 and GLP, nerolidol was administered via the diet to Wistar rats at 0, 1500, 4000, 12000 ppm for 37 days (males) and 58 days (females), (BASF 96R0466/09052).

General systemic toxicity was noted in the parental males at 12000 ppm and in the parental females at 12000 and 4000 ppm. Salient findings were distinct decreases in food consumption and body weights/ body weight gain (which were most severe in females during gestation and lactation) as well as clinical pathological findings. Pathology revealed the liver to be the target organ of toxicity, showing increased weights in both sexes and central hepatocellular hypertrophy and central fatty change in females.

Nerolidol showed no adverse effects on fertility of the parental animals of both genders at 1500, 4000 and 12000 ppm. Nerolidol caused no impairments of the reproductive performance. Mating behaviour, conception, gestation, parturition, as well as sexual organ weights and gross and histopathological findings of these organs were not influenced.

Developmental toxicity was observed in terms of a slight but statistically significant reduction of offspring body weights/body weight gain exclusively at the top dose level of 12000 ppm. Slightly lower number of implants and a subsequent litter size reduction (within the historical control values) was found in the 12000 ppm dose group without reaching statistical significance and the biological relevance of this finding is questionable. There were no other adverse findings in the offspring, which might indicate a selective influence of the test compound on postnatal development. This probably temporary developmental delay is considered to be secondary to the clearly impaired well-being of the mothers in this dose group.

 

Taken together, the NOAEL for general toxicity in parental animals has been set to 4000 ppm (corresponding to about 270 mg/kg bw/d.) for males and 1500 ppm (corresponding to about 105, 120 or 193 mg/kg bw/d) for non-pregnant, pregnant or lactating females, respectively.

A NOAEL >= 12000 ppm has been set for fertility and reproductive performance, corresponding to about 755 mg/kg bw/d in males and 705, 824 or 1194 mg/kg bw/d in non-pregnant, pregnant or lactating females, respectively.

For developmental toxicity a NOAEL has been set at 4000 ppm, corresponding to about 270 mg/kg bw/d in males and 279, 340 or 468 mg/kg bw/d in non-pregnant, pregnant or lactating females, respectively.

Justification for classification or non-classification

The present data on reproductive toxicity do not fulfill the criteria laid down in 67/548/EEC and 1272/2008/EEC, and therefore, a non-classification is warranted.

Additional information