Hydrocarbons, C10, aromatics, >1% naphthalene

Neurotoxicity

Description of key information

There is no neurotoxicity data available for Hydrocarbons, C10, aromatics, >1% naphthalene. However, data is available for a structural analogue, Hydrocarbons, C10, aromatics and presented in the dossier. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

Hydrocarbons, C10, aromatics

Acute CNS effects: NOAEC (Rat): 600 mg/m³ (based primarily on volatility)

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Effect on neurotoxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

neurotoxicity: acute inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1998/03/11-1998/04/03

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well-documented study report which meets basic scientific principles: GLP.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

no guideline followed

Principles of method if other than guideline:

The aim of the study was to evaluate the behavioral effects of exposure to Hydrocarbons, C10, aromatics in rats. Test methods included selected functional observational measures, automated motor activity assessment and visual discrimination performance.

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

other: WAG/RijCrlBR

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deuschland, Sulzfeld, Germany
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 33-65
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Vehicle:

unchanged (no vehicle)

Details on exposure:

Test atmosphere was generated by pumping liquid Solvarex 10 into stainless steel tubing using peristaltic pumps. The tubing was led through a water bath at 81 deg C and the resulting vapour was transported with an air stream from a compressed air source and added to the main airflow system. The test atmospheres were analysed by a total carbon analyser.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

total carbon analyser

Duration of treatment / exposure:

8 hours

Frequency of treatment:

3 days

Remarks:

Doses / Concentrations:
0 (air), 200 mg/m3 (35ppm), 600 mg/m3 (110ppm), 2000 mg/m3 (365ppm)
Basis:
nominal conc.

No. of animals per sex per dose:

8 animals

Control animals:

yes, concurrent no treatment

Details on study design:

Animals were exposed to the test atmosphere in modified H100 inhalation chambers Hazleton System Inc., USA. Each chamber was fitted with a manometer that allowed monitoring the slightly negative pressure inside. Three test groups (with one control) comprising of 8 rats each were exposed to Solvarex 10 at different concentrations including: 0 (air), 0.2 g/m3 (35ppm), 0.6 g/m3 (110ppm), 2.0 g/m3 (365ppm). Animals were exposed to the test atmosphere 8 hours/day for 3 consecutive days. All rats were checked for health and viability at least once daily. Body weight was recorded during randomization on days of testing.

Details on results:

Results of the behavioral tests indicated Hydrocarbons, C10, aromatics induced disturbances in measures from different functional domains including gait abnormalities and visual discrimination performance. Some gait abnormalities were observed throughout the 3-day exposure period in rats exposed to the highest concentration of Hydrocarbons, C10, aromatics (2000 mg/m3). The severity of these abnormalities was low to moderate. Effects were also observed on measures of learned performance. Exposure to the highest concentration of Hydrocarbons, C10, aromatics (2000 mg/m3) induced increased latencies to make a correct choice and latencies to obtain water reinforcement, and also increased the variability in the speed of responding. The effects of exposure to Hydrocarbons, C10, aromatics on performance speed were most clearly observed after the first 8-hour exposure period. Also, a small but significant decrease in the number of collected reinforcements was observed in the highest exposure group (2000 mg/m3).

Dose descriptor:

NOAEC

Effect level:

>= 600 mg/m³ air (nominal)

Sex:

male

Remarks on result:

other:

Conclusions:

Short-term, high-level exposure to Hydrocarbons, C10, aromatics induced some mild, reversible neurobehavioral effects on functional observations and measurements of learned performance. Effects were observed during or after 3 consecutive 8 hour exposures at the highest tested concentration of 2000 mg/m3 of Hydrocarbons, C10, aromatics. Exposure to 200 mg/m3 or 600 mg/m3 of Hydrocarbons, C10, aromatics did not induce exposure-related neurobehavioral effects.

Executive summary:

Short-term, high-level exposure to Hydrocarbons, C10, aromatics induced some mild, reversible neurobehavioral effects on functional observations and measurements of learned performance. Effects were observed during or after 3 consecutive 8 hour exposures at the highest tested concentration of 2000 mg/m3 of Hydrocarbons, C10, aromatics. Exposure to 200 mg/m3 or 600 mg/m3 of Hydrocarbons, C10, aromatics did not induce exposure-related neurobehavioral effects.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

600 mg/m³

Study duration:

subacute

Species:

rat

Quality of whole database:

Only study from a structural analogue available for assessment.

Effect on neurotoxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There is no neurotoxicity data available for Hydrocarbons, C10, aromatics, >1% naphthalene. However, data is available for a structural analogue, Hydrocarbons, C10, aromatics and presented in the dossier. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

A study was conducted to evaluate the behavioral effects of rats exposed to hydrocarbons, C10, aromatics (HSPA, 2001). Three test groups (with one control) comprising of 8 rats each were exposed to hydrocarbons, C10, aromatics at different concentrations including: 0 (air), 200 mg/m3 (35ppm), 600 mg/m3 (110ppm), 2000 mg/m3 (365ppm). Animals were exposed to the test atmosphere 8 hours/day for 3 consecutive days. Test methods included selected functional observational measures, automated motor activity assessment and visual discrimination performance.

 

Results of the behavioral tests indicated hydrocarbons, C10, aromatics induced disturbances in measures from different functional domains including gait abnormalities and visual discrimination performance. Some gait abnormalities were observed throughout the 3-day exposure period in rats exposed to the highest concentration of hydrocarbons, C10, aromatics (2000 mg/m3). The severity of these abnormalities was low to moderate. Effects were also observed on measures of learned performance. Exposure to the highest concentration of hydrocarbons, C10, aromatics (2000 mg/m3) induced increased latencies to make a correct choice and latencies to obtain water reinforcement, and also increased the variability in the speed of responding. The effects of exposure to hydrocarbons, C10, aromatics on performance speed were most clearly observed after the first 8-hour exposure period. Also, a small but significant decrease in the number of collected reinforcements was observed in the highest exposure group (2000 mg/m3).

 

Short-term, high-level exposure to hydrocarbons, C10, aromatics induced some mild, reversible neurobehavioral effects on functional observations and measurements of learned performance. Effects were observed during or after 3 consecutive 8 hour exposures at the highest tested concentration of 2000 mg/m3 of hydrocarbons, C10, aromatics. Exposure to 200 mg/m3 or 600 mg/m3 of hydrocarbons, C10, aromatics did not induce exposure-related neurobehavioral effects.

Justification for classification or non-classification

No chronic neurotoxicity specific studies for C10-C12 Aromatic fluids were located. However, in a 13 week subchronic inhalation study, the toxicity of C10-C12 Aromatic fluids was examined in both rats and dogs (Carpenter, 1977). There were no neurological effects noted by the researchers in either species. There were no abnormalities noted in the histopathological examination of the brain or in the peripherial nerves for either species. The NOAEC for rats and for dogs was determined to be > 0.38 mg/L, which was the highest concentration tested. Therefore, C10-C12 Aromatic hydrocarbon fluids are not likely to cause neurotoxicity.

 

C10 aromatic hydrocarbon fluids are classified as a H336: Vapors may cause drowsiness and dizziness, due to acute CNS depression.

 

Carpenter CP, Geary DL Jr, Myers RC, Nachreiner DJ, Sullivan LJ, King JM. 1977. Petroleum hydrocarbon toxicity studies XIV. Animal and human response to vapors of "high aromatic solvent". Toxicol Appl Pharmacol. 1977 Aug;41(2):235-49.