Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
Based on comparable absorption, distribution, metabolism and excretion of furfural and furfuryl alcohol it is considered appropriate to consider data for furfural alcohol for systemic toxicity.  
Two 14 week studies have been conducted, one in mice and one in rats, to investigate the effects of repeated exposure to furfuryl alcohol by inhalation and included evaluation of vaginal cytology and sperm analysis. No treatment-related effects on estrous cyclicity, sperm number or motility were detected and no potential for impaired reproductive performance indicated.
Additional information
Short description of key information:
There are no fertility or reproduction studies available for furfural. From the determination of estrus cyclicity and sperm analysis conducted as part of 14 week studies of repeat exposure to fufuryl alcohol by inhalation, there is no indication of any adverse effect in rats or in mice that would impair reproductive performance. The limited data on organ weights and histology from subchronic studies of the oral administration furfural do not indicate any adverse effects on the reproductive organs.

Effects on developmental toxicity

Description of key information
An OECD Guideline 414 developmental toxicity study of furfural in rats is available and demonstrates no evidence of developmental toxicity at maternally toxic dose levels.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
100 mg/kg bw/day
Additional information

The available OECD Guideline 414 developmental toxicity study in rats used the oral (gavage) route of administration for furfural (Nemec, 1997). This key study was described in the Risk Assessment Report of 2-Furaldehyde (Furfural) published as a final version by the EU in 2008.

Mated female rats were dosed with 0, 50, 100 or 150 mg/kg bw/day furfural from days 6 to 15 of gestation. The highest dose level of 150 mg/kg bw/day produced maternal lethality and was unsuitable for the evaluation of developmental toxicity. The maternal NOAEL was considered to be less than 50 mg/kg bw/day, based on clinical observations (exophthalmia and tremors) at all dose levels. The developmental NOAEL was considered to be 100 mg/kg bw/day, the highest dose level that could be evaluated; no teratogenicity was observed at this dose level.

The CMR Working Group concluded that furfural should not be classified for reproductive toxicity under Directive 67/548/EEC (November 2003).

Toxicity to reproduction: other studies

Additional information

For female rats and mice, at approximately 18 weeks of age and following 12 weeks repeated exposure to furfuryl alcohol at concentrations of up to 32 ppm, vaginal samples were collected for up to 12 consecutive days prior to the end of the study. The period of exposure to furfuryl alcohol was consistent with the pre-mating period for a reproduction study and the animals were of a similar age. The vaginal samples were evaluated for the relative frequency of estrous stages and for estrous cycle length and the stage of estrous cycle was determined (diestrus, proestrus, estrus or metestrus).

For male rats and mice, at approximately 18 weeks of age and following 14 weeks repeated exposure to furfuryl alcohol at concentrations of up to 32 ppm, sperm samples were collected at the end of the study. The period of exposure to furfuryl alcohol was slightly longer than required for the pre-mating period for a reproduction study and the animals were of an equivalent age for mating. The samples were evaluated for sperm count and motility and the left cauda epididymis, left epididymis, and left testis were weighed. There was no effect of furfuryl alcohol on estrous cyclicity or on sperm parameters in rats or mice at exposure concentrations of up to 32 ppm (equivalent to 128 mg/m3).

Very limited data available from studies of 13 week oral administration of furfural to rats and to mice did not indicate the potential for the chemical to adversely affect any of the reproductive organs at dose levels that did induced lethality/toxicity and neither did the data obtained from the subsequent two year studies. However, it is recognised that the two year studies provide little relevant data for defining the potential effect of furfural on reproduction.

 

Justification for classification or non-classification

The assessment of developmental toxicity in rats exposed to furfural by oral gavage confirmed a lack of effect on the foetus in the presence of maternal toxicity. The comparable absorption, distribution, metabolism and excretion of furfural and furfuryl alcohol allow for read across to other relevant studies. Exposure to furfuryl alcohol by inhalation for 14 weeks produced no adverse effect on sperm count or motility or on estrous cyclicity in rats or in mice. Although there are no reproduction data available to confirm the lack of effect, the existing data indicate that furfural is not a reproductive toxicant.

These data provide adequate information from which to assess the potential of furfural to induce reproductive or developmental effects and to conclude that classification under the DSD or CLP is not warranted.