Registration Dossier

Administrative data

Description of key information

Ethanethiol was not identified as a dermal irritant in rabbits following 4 hour occlusive exposures (Latven, 1977). 
No ocular irritation data were available for ethanethiol, however read-across eye irritation studies from the related substances propane-1-thiol and propane-2-thiol, were identified. Propane-1-thiol was observed to be slightly irritating (although not to a degree that would trigger classification; Moon, 1981) while propane-2-thiol was not considered to be an ocular irritant (Latven, 1977). Based on weight of evidence ethanethiol is not considered to be an eye irritant.
Key data was available for respiratory irritation and based on data available from one study in mice, ethanethiol is not considered to be a respiratory irritant (Pence, 1983; see Section 7.9.3 for EPSR).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was classified as reliable with restrictions because it was an acceptable, well-documented study report which meets basic scientific principles.
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: 49CFR173.240
GLP compliance:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
other: albino
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 0.845 g/mL
Duration of treatment / exposure:
4 hour(s)
Observation period:
3 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: trunk
- Type of wrap if used: gauze patch

Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 4 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: overnight
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 4 hours
Score:
0
Max. score:
4

Initial skin contact evoked a mild pain reaction, when exposures were  terminated at four hours, moderate erythema (score 2) was present at all  of the treated sites; this
dissipated completely overnight. No other signs of skin irritancy could be discerned.

Interpretation of results:
slightly irritating
Remarks:
Migrated information (Not Classified) Criteria used for interpretation of results: EU
Conclusions:
Ethanethiol was found to be slightly irritating to the skin of rabbits, but this irritation was not sufficient to trigger classification (Latven, 1977).
Executive summary:

In a key primary dermal irritation study (Latven, 1977), six albino rabbits were dermally exposed to 0.5 millilitres of ethanethiol under occlusive wrap for 4 hours. The animals were subsequently observed for a period of 3 days.

Initial skin contact was found to elicit a mild pain reaction and moderate erythema (2) was observed at all treated sites at the end of the 4-hour exposure period. However, erythema was reversible and observed to have dissipated completely by the following morning. No other signs of treatment-related irritation or toxicity were observed. Ethanethiol was not considered to be a dermal irritant.

This study received a Klimisch score of 2 and is classified as reliable with restrictions because it was an acceptable study report which meets basic scientific principles.

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:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with national standard methods with acceptable restrictions
Reference:
Composition 0
Qualifier:
no guideline followed
Principles of method if other than guideline:
Draize method
GLP compliance:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
other: Albino
Details on test animals or tissues and environmental conditions:
No detail available
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
Not rinsed
Observation period (in vivo):
10 min and 1, 2, 3, 4, 24, 48 and 72 hours
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: No data
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24+48+72h
Score:
0.1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0
Max. score:
2
Irritant / corrosive response data:
The only effec was conjunctival inflammation with or without chemosis. Neither the cornea nor the iris was effected
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a pre-GLP study conducted using a protocol similar to OECD test guideline propane-2-thiol was not irritating to the eyes of rabbits (Latven, 1977).
Executive summary:

In a pre-GLP study conducted using a protocol similar to OECD test guideline (Latven, 1977), a 0.1 ml dose of propane-2 -thiol was instilled into one eye of six rabbits. Irritation was scored at 10 min and 1, 2, 3, 4, 24, 48 and 72 hours. Conjunctival redness and chemosis were noted in an eye irritation study. The responses recovered within 24 hours in five of six rabbits while the sixth animal recovered within 48 hours. Propane-2-thiol is not an eye irritant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin Irritation

In a key primary dermal irritation study (Latven, A. R., 1977c; Klimisch score = 2), six albino rabbits were dermally exposed to 0.5 millilitres of ethanethiol under occlusive wrap for 4 hours. The animals were subsequently observed for a period of 3 days. Initial skin contact was found to elicit a mild pain reaction and moderate erythema (grade 2) was observed at all treated sites at the end of the 4-hour exposure period. However, erythema was reversible and observed to have dissipated completely by the following morning. No other signs of treatment-related irritation or toxicity were observed. Ethanethiol was not considered to be a dermal irritant.

Eye Irritation

No data evaluating the ocular irritation potential of ethanethiol were identified. However, two key read across studies evaluating the ocular irritation potential of two other Category members, propane-1-thiol and propane-2-thiol were identified. Several criteria justify the use of the read across approach to fill data gaps for ethyl mercaptan using information on propane-1-thiol and propane-2 -thiol. Propane-1-thiol and propane-2-thiol, like ethanethiol, are C2,4-alkyl mercaptans and have similar physiochemical properties. Hence, their toxicological properties are also expected to be similar to those of ethanethiol.

In a key read across eye irritation study (Moon, 1981b; Klimisch score = 2), 0.1 milliliters of propane-1-thiol was instilled into the conjunctival sac of the right eye of 6 young adult New Zealand white rabbits (male) for 4 seconds. The eyes were not washed subsequent to exposure and the left eyes served as control.  Animals were observed for a period of 7 days post exposure and eye irritation was scored by the method of Draize. At the 1-hour scoring interval, five of six animals showed slight to dark redness. Discharge was observed in four of six animals; chemosis was visible in three of the six animals; and one animal was observed to have a lesion.  By the 24-hour reading, three of six animals had returned to normal and remained so through study termination.  Two of three affected rabbits showed redness through the 4-day scoring interval and one of these animals (lesion-bearing) exhibited chemosis through the 72-hour reading.  The remaining animal had redness that resolved after the 24-hour reading. At study termination (day 7) the treated eyes of all animals were observed to be normal.The mean irritation scores were 8.0, 2.3, 0.3, and 0.3 for 1, 24, 48, and 72 hours respectively.The mean overall Draize irritation score (24, 48, and 72 hours) was 3.3. Based on these observations, propane-1-thiol was considered to be irritating to the eyes of rabbits.

In a key read across study (Latven, A.R., 1977b; Klimisch score = 2) 0.1 milliliters of propane-2-thiol was instilled into one eye of six albino rabbits.  Rabbit eyes were left unwashed and animals were observed for a period of 72 hours post-exposure.  Eye irritation was scored using the method of Draize.  Mild and reversible conjunctival redness and chemosis were observed in exposed animals with full recovery occurring within 24 hours in 5 of 6 rabbits, and full recovery occurring within 48 hours in the sixth rabbit.  The mean (24, 48, and 72 hours) iris, cornea, and chemosis scores were 0 while the mean score for conjunctival irritation was 0.1.  Based on this data, propane-2-thiol was not considered to be an ocular irritant.

Respiratory Tract Irritation

One key study in mice was available to evaluate the respiratory irritation potential of ethanethiol .

In a key respiratory tract irritation study (Pence, 1983; Klimisch score = 2, see Section 7.9.3 for the EPSR), 4 male outbred SPF mice were exposed via head only inhalation to 1.93 milligram per liter (1930 mg/m3) of ethanethiol for two periods of one minute exposures separated by a ten minute exposure to room air. Animals were then observed for five minutes or until the respiratory rate returned to pre-exposure rates. The test material was applied as a vapor in a head only exposure chamber attached to a plethysmograph. Only three mice were exposed because one mouse was reported to have died prior to exposure. None of the three mice demonstrated changes in respiratory rate during either one minute exposures to 1.93 mg/L ethanethiol. Based on the results the authors concluded that the test material is not an irritant when 1.93 mg/L (1930 mg/m3) is inhaled by mice. Compound-induced corrosion was not reported.

This finding is supported by the read-across repeated dose toxicity studies on butane-2 -thiol, butane-1 -thiol and 2 -methylpropane-2 -thiol, which did not show a consistent pattern of respiratory irritation (Kim, 2009; Ulrich, 1982 and Ulrich, 1984).

Read-Across Justification

To reduce animal testing REACH recommends to make use of a read-across approach where appropriate based on the high accordance in properties relevant for the specific endpoint.

There are no data on eye irritation for ethanethiol, therefore good quality studies on the related substances propane-1-thiol and propane-2-thiol have been read-across to assess the potential for ethanethiol to cause eye irritation.

The low molecular weight aliphatic alkylthiols are volatile organic liquids of moderate aqueous solubility and low n-octanol-water partition coefficient. The substances all contain a single thiol (-SH) functional group. The acid dissociation constant (pKa) of the thiol group is approximately 10 therefore the substances can be considered as weak acids which will not be significantly ionised at physiologically relevant pH. With regard to eye irritation it is acceptable to predict that pH difference between ethanethiol and the read-across substances, propane-1 -thiol and propane-2 -thiol, would not be sufficient to cause a different outcome in eye irritation studies. For skin and eye irritation there is a pattern of non-classifiable, slight irritation or no irritation for ethanethiol (skin only) and all of the read-across substances. The slight irritation observed in some skin and eye studies reflects the weak acid properties of these substances. Therefore it is predicted that ethanethiol is not irritating to the eyes.



Justification for selection of skin irritation / corrosion endpoint:
This study was the only reliable study available for skin irritation. It is reliable with restrictions because it was an acceptable, well-documented study report which meets basic scientific principles, but was not conducted in compliance with GLP.

Justification for selection of eye irritation endpoint:
The key study was conducted using a study protocol comparable with OECD 405, and in compliance with GLP.

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Ethanethiol does not meet the criteria for classification and labelling according to Regulation (EC) No 1272/2008.

Ethanethiol does not meet the criteria for classification and labelling as an eye irritant according to Regulation (EC) No 1272/2008, based on read-across from related substances which were not irritating to the eyes of rabbits.

Ethanethiol does not meet the criteria for classification and labelling as a respiratory irritant as defined by Regulation (EC) No 1272/2008.