Butane-1,3-diol

Endpoint summary

Description of key information

Skin irritation:
Human data reveal no or only minimal skin irritating properties of the undiluted substance or a 50% aqueous solution. This is supported by animal studies with neat substance, where no or only minimal signs of skin irritation are documented, which is not.
Eye irritation: relevant with respect to classification.
The key study documents a slight irritating effect in the eyes of rabbits, and several further animal studies showed no or only minimal eye irritation. Human data are restricted to a short remark in a handbook, which reports that the substance caused stinging, when it was applicated to the human eye and there was a rapid complete relief after rinsing-off the material.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study was performed according to a national guideline (Official French methods for cosmetics and beauty products, Annex I), which is similar to the guidelines EU B4 and OECD 404, but report lacks details in data presentation (e.g. insufficient information on purity of the test substance), no individual scores available.

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

Official French methods for cosmetics, Annex I

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

male albino rabbits
animal weight: 2.5-3.5 kg
animal housing in individual cages
minimal time of acclimatisation: 8 h

Type of coverage:

occlusive

Preparation of test site:

other: shaved, tested on intact or abraded skin in parallel

Vehicle:

unchanged (no vehicle)

Controls:

other: internal controls

Amount / concentration applied:

100% (undiluted)

Duration of treatment / exposure:

24 h, single application, occlusive

Observation period:

at end of exposure and 48 h thereafter (24 h and 72 h after start of application, respectively)

Number of animals:

6 males

Details on study design:

Albino rabbits (2.5-3.5 kg) were shaved on the back and the left and right flanks (approx. 14 x 14 cm). After a recovery period of 24 h, the animals skin of the right flank was abraded with a sterile blade (three incisions of 3 cm length in approx. 0,5 cm distance). These incisions did not affect the dermis.
0.5 ml of the test substance each were put on two occlusive "Neodermotest" patches, which were placed on the right flank (one on intact skin, the other on the abraded area), fixed with absorbent gauze and adhesive tape. The animals were kept in immobilisation cages for 24 h and afterwards the test patches were removed. The untreated left flank served as control for evaluation of the skin irritating action.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 h after appliccation

Score:

0.08

Max. score:

8

Reversibility:

no data

Irritant / corrosive response data:

The primary skin irritation index of undiluted test substance was 0.08 (not irritating)

The cumulative irritation at repeated application (6 weeks of exposure) was also tested. The mean maximum cutaneous index (MMII) was as follows:

10% aqueous solution: 0 (very well tolerated)

100%: 0.58 (relatively well tolerated)

Interpretation of results:

GHS criteria not met

Conclusions:

Under these test conditions there was no acute skin irritation with the undiluted test substance.

Executive summary:

Rabbits were exposed dermally to single doses of undiluted test substance. No acute irritation was observed (Guillot et al., 1982).

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1951

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Information on purity of the substance not stated, several study details are lacking, deviations from guideline requirements

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

primary skin irritation test

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

Albino rabbits

Type of coverage:

open

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.01 ml neat substance

Duration of treatment / exposure:

24 h

Observation period:

obervation at end of exposure

Number of animals:

5

Details on study design:

0.01 ml of the undiluted substance were applied to the shaved abdominal skin.

Irritation parameter:

other: reaction grade

Basis:

other: unknown

Time point:

other: unknown

Score:

ca. 1

Max. score:

6

Reversibility:

no data

Remarks on result:

other: no reaction

Irritant / corrosive response data:

reaction grade 1 (no reaction)

no skin reaction from undiluted sample observed

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, there was no skin irritation.

Executive summary:

When rabbits were exposed dermally to the undiluted test substance for 24 h, no skin irritation was observed (Smyth et al.,1951).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study was performed according to a national guideline (Official French methods for cosmetics, Annex II), which is similar to the guidelines EU B5 and OECD 405, but lacks details in data presentation (e.g. insufficient information on purity of the test substance).

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

Official French methods for cosmetics, Annex II

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

male albino rabbits with healthy eyes (without defects)
animal weight: 2 kg

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

18 h

Observation period (in vivo):

Evaluation of effects was performed after 1 h, 24 h, 2, 4 and 7 days.

Number of animals or in vitro replicates:

6 males

Details on study design:

The test substance was instilled under the lower lid of one eye and the lids were held closed for several seconds to prevent loss of the test substance.
The animals were kept immobilised for 18 h, and then transferred to their cages.
For the improved detection of opacity, the eyes were stained with 2% aqueous fluorescein solution. Examination was performed by an opthalmoscope and a retinographe.
The untreated eye served as control.

Irritation parameter:

other: acute ocular irritation index

Basis:

mean

Time point:

other: 18 h

Score:

12.33

Max. score:

110

Reversibility:

not specified

Irritant / corrosive response data:

The acute ocular irritation index (AOII) of the undiluted test substance was 12.33 (slight irritation)

Interpretation of results:

other: slightly irritating

Conclusions:

Under these study conditions, the test substance was slightly irritating.

Executive summary:

The undiluted test substance produced a slight irritation of the rabbit's eye (Guillot et al., 1982).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

There is no study available which fulfills the requirements of current OECD guidelines. However there is sufficient information available to enable the evaluation of this endpoint in a weight of evidence approach, both from investigations in humans as well as in animals. In a human study 200 volunteers were exposed to 50% aqueous solution of the test substance for 15 times (24 h each) within 5 weeks (exposures on Monday, Wednesday and Friday) by occlusive patch exposures at the upper arm. A mild skin irritation was reported in 2 subjects. After changing the site of application, no further signs of irritation were observed in these individuals (Shelanski, 1973, 1974).

The result of this study is supported by another clinical trial, where 37 and 39 volunteers were exposed to neat substance for 24 h by occlusive or semiocclusive patches, respectively. Only one subject of the semiocclusive group showed mild skin irritation (CTFA, 1985). Also, no skin irritation was reported in another study with human volunteers after single and repeated exposure (Loeser, 1949).

Additionally, in an animal study with rabbits, which were exposed for 24 hours on intact or abraded skin and which were evaluated immediately after end of exposure or 48 hours after end of exposure, no skin irritation was observed (Guillot et al., 1982). Smyth et al. (1951) also reported that no skin irritation was observabed in rabbits after 24 hour exposure to neat substance. Further studies with animals of several species (rat, rabbit, guinea pig), which are insufficiently documented for evaluation, consistently reported no or only minimal skin irritation (CTFA, 1985; Fischer et al., 1949, ; Loeser, 1949). Overall, various data available from humans and animals provide consistent information indicating that butane-1,3 -diol is not or only veryl slightly irritating to skin and that no classification for this endpoint is required.

Eye irritation:

Immediate stinging was reported after application of one tiny drop into the human's eye, irrigating with water brought a rapid complete relief (Grant, 1974). The undiluted substance caused only slight irritation in the eye of rabbits (Guillot et al., 1982; key study). A (incompletely reported) Draize test (Watanabe et al., 1949) and other animal data (Carpenter et al., 1946; CTFA, 1985; Fischer et al., 1949; Loeser, 1949; Smyth et al., 1951) showed no eye irritating potential.

Justification for classification or non-classification

Based on the available data, according to Directive Regulation (EC) No 1272/2008 no classification is required with respect to skin or eye irritation.