Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

No data are available for the reproductive toxicity endpoint. A waiver is proposed for the 2-generation reproductive toxicity study, in line with Column 2 of Annex IX of the REACH Regulation and consistent with current guidance.  The 2-generation study is triggered at this tonnage band by alerts or concerns for reproductive toxicity from available data, QSAR or from related substances.  The key repeated dose toxicity study for hexyl acetate was a read-across 90-day inhalation study performed with the structurally related substance butyl acetate.  This study included assessment of testes weight, histopathology and sperm counts.  No clear effects of treatment were apparent on these parameters.  There is therefore no specific alert or concern over the reproductive toxicity of hexyl acetate.


Short description of key information:
No data are available for the reproductive toxicity endpoint.

Effects on developmental toxicity

Description of key information
Studies using gavage administration in the rat are available for octyl acetate and n-hexanol. Studies using inhalation exposure in the rat are available for n-butyl acetate and hexanol
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
200 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Studies using gavage administration in the rat are available for octyl acetate and n-hexanol. Both studies indicate possible mild developmental toxicity at the limit dose of 1000 mg/kg bw/d, however the resulting NOAEL is lower for the n-hexanol study as a consequence of dose spacing
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
3 800 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
Studies using inhalation exposure in the rat are available for n-butyl acetate and hexanol..
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

A weight of evidence approach is used for developmental toxicity, using studies in the rat performed with a number of read-across substances using oral (gavage) dosing and inhalation exposure.

A gavage study performed with octyl acetate (Daughtrey et al, 1989) reported maternal toxicity at dose levels of 500 and 1000 mg/kg bw/d; toxicity at the highest dose level included maternal mortality. Developmental toxicity in this study was limited to a possible slight increase in the incidence of vertebral variations/malformations at the highest dose level only.

A gavage study performed with n-hexanol (Rodwell et al, 1988) reports maternal toxicity (clinical signs and reduced weight gain) and a slight reduction in foetal weight at the highest dose level of 1000 mg/kg bw/d. No effects were seen at the next dose level of 200 mg/kg bw/d.

An inhalation study performed using n-butyl acetate (Saillenfait et al, 2007) reported maternal toxicity (reduced weight gain and/or food consumption at exposure levels of 1000, 2000 and 3000 ppm); developmental toxicity was limited to reduced foetal weight at the highest concentration.

An inhalation study performed using hexanol (Nelson et al, 1989; 1990) showed no maternal toxicity at an exposure level of 3800 mg/m3. A slight increase in resorption rate seen at this exposure level was within the control range.

The results of developmental toxicity studies with read-across substances (analogues, metabolites) indicate possible mild developmental toxicity only at very high and maternally toxic dose levels. There is no evidence for selective developmental toxicity.


Justification for selection of Effect on developmental toxicity: via oral route:
A weight of evidence approach is followed for this endpoint.

Justification for selection of Effect on developmental toxicity: via inhalation route:
Studies using inhalation exposure in the rat are available for n-butyl acetate and hexanol. The lower endpoint is from the hexanol study

Justification for classification or non-classification

There is no evidence for reproductive toxicity or for specific developmental toxicity in studies performed with read-across substances; developmental toxicity was mild and seen only at very high and maternally toxic dose levels. No classification for reproductive toxicity is therefore proposed according to the CLP Regulation.

Additional information