Registration Dossier

Administrative data

Description of key information

Two experimental in vivo studies with rabbits reported skin irritating effects for tetrahydronaphthalene (Hüls AG 1984, Carpenter 1949) also in a dermal toxicity study a skin irritating effect was observed in rats (Clark, 1984). Two experimental studies with rabbits showed no or mild and reversible eye irritation (Hüls AG 1984; Carpenter 1949).

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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
Smyth HF Jr, Carpenter CP (1944): The place of the range finding test in the industrial toxicology laboratory. J. Ind. Hyg. Toxicol. 26, 269-273 and subsequent updates
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Type of coverage:
not specified
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
ADMINISTRATION/EXPOSURE 
- Total volume applied: 0.01 ml
- undiluted
Duration of treatment / exposure:
24 hour(s)
Number of animals:
5
Details on study design:
ADMINISTRATION/EXPOSURE 
- Area of exposure: clipped belly
EXAMINATIONS
- Scoring system: Draize et al. (1944): Methods for the study of  irritation and toxicity of substances applied topically to the skin and  mucous 
membranes. J. Pharmacol. Exper. Therap. 82, 377; maximum scores: 10
- Examination time points: 24 hours after application
Irritation parameter:
erythema score
Basis:
mean
Score:
4
Max. score:
10
Remarks on result:
other: moderate to marked erythema
Other effects:
Symptoms: 
Moderate to marked erythema, intensity comparable to 2-ethyl  hexyl acetate Irritation index: 4/10, where 4 is a slight erythema  resulting of 
exposure to an undiluted sample of the test substance.
Conclusions:
Under the conditions of the study, Tetrahydronaphthalen was irritating to the skin.
Executive summary:

The application of 0.01 mL of the undiluted tetrahydronaphthalene to the clipped skin of the rabbit produced moderate to marked erythema of an intensity comparable to that induced by 2 ethyl-hexylacetate which is representative of grade 4 compounds.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
Test method used as described in the publication
GLP compliance:
not specified
Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
TEST ORGANISMS: 
- Weight at study initiation: 225-306 g
- Strain: COBS/Wistar
- Sex: male
Type of coverage:
open
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
ADMINISTRATION: 
- undiluted
- Vehicle: none
- Total volume applied: maximum 2.0 ml per rat
Duration of treatment / exposure:
24 h
Number of animals:
2
Details on study design:
ADMINISTRATION: 
- Area covered: shaved, approximately 20-25 % of body surface
- Occlusion: no
-undiluted
Irritation parameter:
other: No irritation index provided
Other effects:
No irritation index provided

Mild skin irritation was reported.

Conclusions:
Mild skin irritation was reported.
Executive summary:

In an acute dermal toxicity test two male rats each received a dermal doses of 1.8 g, 3.6 g or 7.3 g Tetrahydronaphthaline applied undiluted to the shaved skin with unoccluded dressing for 24 h.

No adverse systemic effects were noted during 14 days observation period.

Local effects were summarised as mild skin irritation.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1984-11-13 to 1984-11-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions: In deviation from OECD TG 404 occlusive dressing was used.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: Small white Russian, Chbb-SPF
Details on test animals or test system and environmental conditions:
TEST ANIMALS: 
- Strain: Small white Russian, Chbb-SPF
- Sex: male and female
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Weight at study initiation: 2.2-2.5 kg
- Number of animals: 3 males, 3 females
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
ADMINISTRATION/EXPOSURE 
- Vehicle: none
- Total volume applied: 0.5 ml
Duration of treatment / exposure:
4 hour(s)
Observation period:
Postexposure period: 14 days
Number of animals:
3 per sex
Details on study design:
ADMINISTRATION/EXPOSURE 
- Area of exposure: 6 cm²
- Occlusion: mull patch, polyethylene film, elastic dressing
- Postexposure period: 14 days
- Removal of test substance: washing with warm water
EXAMINATIONS
- Scoring system: according to Draize
- Examination time points: 1, 24, 48, 72 hours, 6, 9, 11, and 14 days  after administration of the test substance
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1, 24, 48, 72 h
Score:
4.55
Max. score:
8
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 h
Score:
3.11
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 h
Score:
1.56
Max. score:
4
Reversibility:
not fully reversible within: 14 days

AVERAGE SCORE 
- Erythema: 3.11
- Edema:  1.56
- Irritation index: 4.55/8 = moderately irritant
REVERSIBILITY: not complete within 14 days

Irritant response data for each animal at each observation time

Score at time point / Reversibility

Erythema

Edema

Max. score: 4

Max. score: 4

60 min

2/2/2/3/2/2

2/2/2/2/2/2

24 h

3/3/3/3/3/3

1/3/2/2/1/1

48 h

3/4/3/3/3/3

1/3/1/2/1/1

72 h

3/4/3/3/3/3

2/3/1/1/1/1

6 days

3/3/2/2/2/2

2/3/1/1/1/1

9 days

Eschar formation for all animals

11 days

Eschar formation for all animals

14 days

Eschar formation for all animals

Average 24h, 48h, 72h

3.11

1.56

Reversibility

Not completely reversible

Conclusions:
According to the outcome of the skin irritation study tetrahydronaphthalene is moderately irritant to skin of rabbits.
Executive summary:

In a primary skin irritation test with three male and three female rabbits tetrahydronaphthalene was applied with occlusive dressing to the shaved back skin at a dose level of 0.5 mL per animal for 4 h. Residual test substance was washed of with warm water. Skin reaction were scored according to OECD criteria at 1h, 24h, 48h, 72h and 6d, 9d, 11d and 14d after application.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1984-11-13 to 1984-11-19
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: Small white Russian, Chbb-SPF
Details on test animals or tissues and environmental conditions:
TEST ANIMALS: 
- Strain: Small white Russian, Chbb-SPF
- Sex: male and female
- Source: Dr. Karl Thomae GmbH, Biberach
- Weight at study initiation: 2.2-2.7 kg
- Number of animals: 3 males, 3 females
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
- undiluted
- Amount applied: 0.1 ml
- Controls: untreated (left) eye
Duration of treatment / exposure:
not rinsed
Observation period (in vivo):
 Ophtalmoscopic examination: 1, 24, 48, 72 hours, 6 days after treatment
Number of animals or in vitro replicates:
6
Details on study design:

EXAMINATIONS
- Ophtalmoscopic examination: 1, 24, 48, 72 hours, 6 days after treatment
- Scoring system: Draize (1959); Appendix VI of 79/831/EEC
- Tool used to assess score: Na fluorescein / ophthalmic lamp / visual  inspections
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
5.17
Max. score:
110
Reversibility:
fully reversible within: 6 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24,48, 72 h
Score:
0
Max. score:
80
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
10
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
1.33
Reversibility:
fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.22
Reversibility:
fully reversible within: 48 h
Conclusions:
The rabbits In the study showed only slight to mild but also reversible conjunctival effects. Tetrahydronaphthalene was not considered to be an eye irritant.
Executive summary:

In a primary eye irritation study 0.1 mL of undiluted tetrahydronaphthalene was instilled into the conjunctival sac of one eye of three male and three female young adult White Russian rabbits. Eyes were not rinsed. Animals were observed for 6 days. 

Cornea and iris were not affected. Slight to mild and reversible conjunctival effects were observed. In this study, tetrahydronaphthalene was not an eye irritant.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
Carpenter CP, Smyth HF (1946): Chemical burns of the rabbit cornea, Am. J. Ophthalmol. 29, 1363-1372
GLP compliance:
no
Species:
rabbit
Strain:
other: Albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS: 
- Strain: Albino, not specified
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
ADMINISTRATION/EXPOSURE 
- Exposure period: 18 - 24 h
- undiluted
- Amount applied: 0.5 ml
Number of animals or in vitro replicates:
5
Details on study design:
Comment: not rinsed
EXAMINATIONS
- Scoring system: maximum 10 scores
- Tool used to assess score: eye examined in strong diffuse daylight,  then stained with fluorescein
Irritation parameter:
overall irritation score
Score:
1
Max. score:
10
Reversibility:
not specified
Other effects:
- Overall irritation score: 1  
 "No damage"
Conclusions:
Under conditions of this study conducted with rabbits tetrahydronaphthalene is not considered to be an eye irritant.
Executive summary:

In a primary eye irritation study 0.5 mL of undiluted tetrahydronaphthalene was instilled into the eye of albino rabbits. Animals were observed for 3 days. 

Cornea and iris were not affected. Very mild and reversible conjunctival effects were observed. In this study, tetrahydronaphthalene was not an eye irritant..

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Cited from SIAR for19 (19-22 October 2004):

Skin irritation

Studies in Animals

In a study according to OECD TG 404 with rabbits (Small white Russian), undiluted 1,2,3,4-tetrahydronaphthalene caused moderate irritation with Draize scores of 3.11 for erythema, 1.56 for edema, and 4.55 in total. Effects were not completely reversible within 14 days (Hüls AG, 1984 b).

Similar irritation intensity was observed in an early and limited study published by Smyth, Carpenter and Weil (1951) as well as by Union Carbide Corp. (1992). They report an irritation index of 4/10 in rabbits 24 hours after application of 0.01 ml 1,2,3,4-tetrahydronaphthalene to the clipped belly of rabbits (no information on occlusion).

Studies in Humans

A skin condition similar to turpentine-induced dermatitis that was eczematous in nature is reported in five painters (four males, one female) that used 1,2,3,4-tetrahydronaphthalene (1 case) or mixtures containing 1,2,3,4-tetrahydronaphthalene as substitutes for turpentine. From the rare occurrence of the symptoms, the author concluded that the persons probably had a high sensitivity (Galewsky, 1922).

Eye Irritation

Studies in Animals

In a study according to OECD TG 405 with rabbits (Small white Russian), undiluted 1,2,3,4-tetrahydronaphthalene caused no significant irritation with Draize scores of 5.17/110. Effects were completely reversible within 6 days (Hüls AG, 1984 a). Similar irritation intensity was observed in an early study published by Smyth, Carpenter and Weil (1951) as well as by Union Carbide Corp. (1992). They report an irritation index of 1/10 in rabbits 18-24 hours after application of 0.5 ml 1,2,3,4-tetrahydronaphthalene to rabbits (not rinsed).

Studies in Humans

Two painters who had been painting for three days with 1,2,3,4-tetrahydronaphthalene-containing varnishes in a poorly ventilated area complained, among others, about irritation of mucous membranes and profuse lacrimation (Arnstein, 1922).

 

Respiratory Tract Irritation

There were no studies available in animals or humans

 

Conclusion

1,2,3,4-Tetrahydronaphthalene was a moderate irritant to the skin (OECD TG 404) but not to the eye (OECD TG 405). However, high exposure from the gas phase may cause irritation of mucous membranes and profuse lacrimation in humans.

 


Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

All available data for skin corrosion/irritation showed that tetrahydronaphthalene has to be classified as skin irritant. Based on our study data for eye irritation, tetrahydronaphthalene does not require classification and labelling as eye irritant (Hüls AG, 1984). However, according to classification according to Annex VI of CLP regulation 1272/2008, tetrahydronaphthalene was classified as eye irritant Cat. 2.