1,2,3,4-tetrahydronaphthalene

Endpoint summary

Description of key information

The acute toxicity of 1,2,3,4-tetrahydronaphthalene was found to be relatively low with an oral LD50 of 2860 mg/kg bw in male rats (Carpenter, 1949), a dermal LD50 of 16800 mg/kg bw in male rabbits (Carpenter, 1949) and no mortalities within 8 hours inhalation of a saturated atmosphere (ca. 1800 mg/m³; male rats; Carpenter, 1949). In man, the chemical is known to produce headache, nausea, vomiting, lacrimation, green-gray urine, and restlessness at high concentrations (Koelsch, 1926).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment. Restriction: Only male animals used

Principles of method if other than guideline:

Method: other: 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

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sherman

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ORGANISMS: 
- Weight at study initiation: 90-120 g
- Feeding: No previous withdrawal of food

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

ADMINISTRATION: 
- Vehicle: Test substance fed by stomach tube as a 20% dispersion in 1%  "Tergitol" 7
- Post dose observation period: 14 days

Doses:

2,000; 2,520; 3,160; 3,980; 7,950 mg/kg bw, maybe additional doses

No. of animals per sex per dose:

10

Control animals:

not specified

Statistics:

Thompson, W.R. (1947): Use of moving averages and  interpolation to estimate median effective dose. Bact. Rev. 11, 115

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 2 860 mg/kg bw

Mortality:

MORTALITY: LD50 = 2.86 (2.58-3.18) g/kg bw

Clinical signs:

other: CLINICAL SIGNS:  Following the doses, the rats exhibited symptoms of sluggishness, prostration, and narcosis. The urine had a brownish coloration.

Gross pathology:

NECROPSY FINDINGS: 
A dose of 7950 mg/kg bw produced severe lung hemorrhage, congestion of the liver, paleness of the kidney with edema in  some instances, 
opacity and adhesions of the intestines. Several of the  livers were jaundiced after the administration of a dosage of 3980 mg/kg  bw. This effect 
was not found at the higher level because of rapid death.  Lower dosage levels produced similar symptoms of lesser intensity.

MORTALITY: LD50 = 2.86 (2.58-3.18) g/kg bw
- Time of death: often delayed 3 to 4 days
- Number of deaths at each dose: 
  2,000 mg/kg bw:  1/10 (day 5)
  2,520 mg/kg bw:  2/10 (day 4)
  3,160 mg/kg bw:  3+2+2/10 (days 1, 3, 4)
  3,980 mg/kb bw:  3+2+3+2/10 (days 1, 2, 3, 4)

Conclusions:

The feeding of the test substance to male albino strain rats resulted in a LD50 =2.86 g/kg bw (2.58 -3.18) based on a 14 day observation period. Thus tetrahydronaphthalene showed low acute toxicity in rats after oral gavage.

Executive summary:

The feeding of tetrahydronaphthalene to male albino strain rats, without previous withdrawal of food, as a 20% dispersion in 1% "Tergitol" resulted in a LD50 =2.86 g/kg bw (2.58 -3.18) based on a 14 day observation period. Clinical signs included sluggishness, prostration and narcosis with deaths often delayed 3 to 4 days. The highest dose of 7.95 g/kg bw produced severe lung hamorrhage, congestion of the liver, paleness of the kidney with edema in some instances, opacity and adhesions of the intestines. Several of the livers were jaundiced after the administration of a dosage of 3980 mg/kg bw. This effect was not found at the higher level because of rapid death. Lower dosage levels produced similar symptoms of lesser intensity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 860 mg/kg bw

Quality of whole database:

Klimisch 2 (reliable with restrictions)

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Documentation very brief

Principles of method if other than guideline:

Method: other: 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

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

male

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

not specified

Details on inhalation exposure:

Animals were exposed to saturated vapor at 20°C or a mist generated at 170°C

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

8 h

Concentrations:

ca. 1.8 mg/l and higher

No. of animals per sex per dose:

6

Control animals:

not specified

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 1.8 mg/L air

Exp. duration:

8 h

Conclusions:

In an inhalation experiment rats showed no mortalities at 8h exposure to saturated vapour at 20°C or a mist generated at 170°C. Thus tetrahydronaphthalene showed low acute toxicity in rats after inhalation.

Executive summary:

Groups of 6 rats each tolerated 8 hour exposure to substantially saturated vapour at room temperature (calculated at 1.8 mg tetrahydronaphthalene per litre air considering a vapour pressure of 34 Pa at 20°C) or to mist generated by aerating the compound while it was heated at 170°C (corresponding to 10.5 mg/L with a vapour pressur of 290 Pa at 170°C)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

1 800 mg/m³ air

Quality of whole database:

Klimisch 2 (reliable with restrictions)

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key 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

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ORGANISMS: 
-male Albino Rabbbits 
-Weight at study initiation: 2,202-2,718 g

Type of coverage:

semiocclusive

Vehicle:

other: undiluted

Details on dermal exposure:

ADMINISTRATION: 
- Area covered: clipped trunk
- Occlusion: impervious flexible film ("vinylite" sheeting)
- Exposure period: 24 hours 
- Observation period: 14 days

Duration of exposure:

24 hours

Doses:

12.6; 15.8; 20.0 g/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Statistics:

Thompson, W.R. (1947): Use of moving averages and  interpolation to estimate median effective dose. Bact. Rev. 11, 115

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 16 800 mg/kg bw

Mortality:

MORTALITY:   
 LD50 = 17.3 (14.5 - 20.6) mL/kg bw
    = 16.8 (14.1 - 20.0)  g/kg bw

Clinical signs:

other: CLINICAL SIGNS:  Upon removal of the covering the skin was erythematous,  on subsequent examination it was necrosed and ultimately leathery and dry.

Gross pathology:

Autopsy revealed pale livers and kidneys and congestion of the pancreas and intestines.

- Number of deaths at each dose: 
  12,600 mL/kg bw:  1/5 on day 4
  15,800 mL/kg bw:  1/5 on day 13
  20,000 mL/kg bw:  1+2+1/5 on days 11, 12, 14

Conclusions:

The LD50 (rabbit) for tetrahydronaphthalene applied to the skin of the rabbit is 17.3 mL/kg bw (=16.8 g/kg bw). Thus tetrahydronaphthalene showed low acute toxicity in rabbits after dermal application.

Executive summary:

The LD50 for tetrahydronaphthalene applied undiluted to the clipped skin of the rabbit trunk under "Vinylit" sheeting for 24h was 17.3 mL/kg bw (14.5 -20.6). Upon removal of the covering the the skin was erythemous, on subsequent examination it was necrosed and ultimately because leathery and dry. Autopsy of victims revealed pale livers, and kidneys and congestion of the pancreas and intestines. The disparity between oral and percutaneous toxicity indicates that tetrahydronaphthalene pentrates quite slowly through the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

16 800 mg/kg bw

Quality of whole database:

Klimisch 2 (reliable with restrictions)

Additional information

Partly cited from SIAR for SIAM 19 (19-22 October 2004):

Studies in Animals

Inhalation and Dermal

Smyth, Carpenter and Weil (1951) reported that six male rats tolerated exposure to saturated atmospheres of 1,2,3,4-tetrahydronaphthalene for eight hours without deaths. A vapor pressure of 34 Pa corresponds to a concentration of 1800 mg/m3. Union Carbide Corp. (1992) added the information that 8 hour exposures to mist, which was generated by aerating the compound while it was heated to 170 °C, were also tolerated without mortalities. Thus one may conclude from this limited study that the LC50 is > 1800 mg/m3. Dermal According to Smyth, Carpenter and Weil (1951) and Union Carbide Corp. (1992), the dermal LD50 of 1,2,3,4-tetrahydronaphthalene in male rabbits is approximately 16,800 mg/kg bw within 14 days post observation. After occlusive exposure of 5 animals each to doses of 12.6; 15.8 and 20.0 g/kgbw for 24 hours, the skin was erythematous, on subsequent examination it was necrotized and ultimately leathery and dry. Autopsy revealed pale livers and kidneys and congestion of the pancreas and intestines.

Oral

In a study with 10 malerats per dose group, the oral LD50 was approximately 2860 mg/kg bw (Smyth, Carpenter and Weil, 1951; Union Carbide Corp., 1992). The doses reported are 2000; 2520; 3160; 3980; 7950 mg/kg bw. Following the doses, the rats exhibited symptoms of sluggishness, prostration, and narcosis. The urine had a brownish coloration. A dose of 7950 mg/kg bw produced severe lung hemorrhage, congestion of the liver, paleness of the kidney with edema in some instances, opacity and adhesions of the intestines. Several of the livers were jaundiced after the administration of a dosage of 3980 mg/kg bw. This effect was not found at the higher level because of rapid death. Lower dosage levels produced similar symptoms of lesser intensity. Since from the other toxicity studies there is no evidence of significant differences in sensitivity between males and females, this study is considered to cover the SIDS endpoint sufficiently.

Studies in Humans

Experience with human exposure to 1,2,3,4-tetrahydronaphthalene was gathered mainly in the years after World War I, when 1,2,3,4-tetrahydronaphthalene was used as a substitute for turpentine. In general, the reliability of the data reported cannot be determined due to lack of documentation. Inhalation Koelsch (1926; insufficiently documented) reports that after occupational application of 1,2,3,4- tetrahydronaphthalene or staying in freshly varnished or waxed rooms, workers complained about headache, nausea, vomiting and irritation of mucous membranes and green-colored urine. In two painters who had been painting for three days with 1,2,3,4-tetrahydronaphthalene-containing varnishes in a poorly ventilated area dark green colored urine was observed as the main symptom beside intense irritation of mucous membranes, profuse lacrimation, headache, and stupor. Reversibility was complete within few days (Arnstein, 1922). After approximately 3 kg wax containing about 1.5 kg 1,2,3,4-tetrahydronaphthalene had been applied in a hospital room of approximately 540 m3 volume, children displayed green colored urine and a marked degree of restlessness. This restlessness was tentatively attributed to a direct effect of 1,2,3,4-tetrahydronaphthalene on the central nervous system without giving further details (Röckemann, 1922; insufficiently documented). Hospital patients on a ward whose floor was recently waxed with a tetralin-based polish and whose windows were closed due to cold weather experienced eye irritation, headache, nausea, diarrhea, and green urine (Badinand, Paufique and Rodier, 1947; insufficiently documented).

Conclusion

The acute toxicity of 1,2,3,4-tetrahydronaphthalene was found to be relatively low with an oral LD50 of 2,860 mg/kg bw (male rats), a dermal LD50 of 16,800 mg/kg bw (male rabbits) and no mortalities within 8 hours inhalation of a saturated atmosphere (ca. 1,800 mg/m3; male rats). In man, the chemical is known to produce headache, nausea, vomiting, lacrimation, green-gray urine, and restlessness at high concentrations

 

.

Justification for classification or non-classification

Based on all available data it can be concluded that the acute toxicity of tetrahydronaphthalene is low. A classification according to CLP regulation 1272/2008 is not required.