Registration Dossier

Administrative data

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

Referenceopen allclose all

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:
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 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).

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:
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 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:
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.