Stoddard solvent

Immunotoxicity

Description of key information

Immunotoxicity. There is no evidence in the available toxicity studies or scientific literate to indicate Immunotoxic effects of the of Stoddard solvent in humans or laboratory animals.  It is therefore considered not scientifically justified to undertake a Immunotoxicity toxicity study in animals.

Key value for chemical safety assessment

Effect on immunotoxicity: via oral route

Link to relevant study records

Reference

Endpoint:

immunotoxicity, other

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Effect on immunotoxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

immunotoxicity: sub-chronic inhalation

Type of information:

other: published data

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

other: Equivalent or similar to OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day)

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Two species were tested in the Kuna experiment: rats and monkeys.Species: monkeyStrain: squirrel monkeys (Saimiri sciureus)Sex: male/femaleIn the O'Regan and Turgeon publication, only rats were tested.Species: ratStrain: Sprague-DawleySex: male

Route of administration:

inhalation

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Scott Model 116

Duration of treatment / exposure:

90 days

Frequency of treatment:

6 hours per day, 5 days per week

Dose / conc.:

1 570 mg/m³ air (analytical)

Dose / conc.:

6 350 mg/m³ air (analytical)

No. of animals per sex per dose:

Kuna publication:rats: 5 groups of 20 males and 20 females monkeys: 5 groups of 4 males and 4 females

Control animals:

yes, sham-exposed

Sacrifice and pathology:

All animals that died spontaneously or were sacrificied were necropsied. At the time of necropsy, organ weights were taken and tissues saved in 10% neutral formalin. Lungs, kidneys, spleen, heart, brain, and bone marrow from the control and high-dose groups were evaluated for histopathology.

Humoral immunity examinations:

All male and female animals from the control and high-exposure level groups were evaluated for the presence and deposition of IgG in the renal glomerulus and lungs.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

not specified

Urinalysis findings:

no effects observed

Gross pathological findings:

not specified

Details on results:

CLINICAL SIGNS AND MORTALITY: Kuna: The death of three rats and three monkeys were not considered to be treatment-related. Two female monkeys in the high dose exhibited emesis after 13 days of exposure.


BODY WEIGHT AND WEIGHT GAIN: No statistically significant difference were observed in body weight changes between controls and any treated group of either species, with the exception of increased mean body weights in male rats in the low-dose group.


HAEMATOLOGY: No statistically significant changes in hematological parameters were noted in male and female squirrel monkeys. Male rats in the high-dose group had a statistically significant increase in thrombocytes. Females in the same group had a statistically significant increase in reticulocyte counts.


URINALYSIS: No exposure-related differences in any of the groups.


ORGAN WEIGHTS: Increased thyroid weights of male monkeys at both dose levels.


CELL VIABILITIES


HUMORAL IMMUNITY EXAMINATIONS: Renal immunofluorescent evaluations of all male and female rats and monkeys displayed no evidence of IgG deposition in the kidneys following the 90-day examination period.


HISTOPATHOLOGY: NON-NEOPLASTIC: Examination of tissues from rats and squirrel monkeys showed no evidence of treatment-related findings, with the excpetion of lesions noted in the kidneys of all male rats. The lesions were characterized by subtle but discernible increases in the incidence and severity of regenerative epithelium and dilated tubules. The tubules were seen to contain protein in their lumens.

Cell viabilities:

not specified

Humoral immunity examinations:

no effects observed

Specific cell-mediated immunity:

not specified

Non-specific cell-mediated immunity:

not specified

Other functional activity assays:

not specified

Other findings:

not specified

Dose descriptor:

NOEL

Effect level:

6 350 mg/m³ air (analytical)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

immunology

Critical effects observed:

not specified

Conclusions:

In the Kuna and Uhlrich study, the NOEL was determined to be equal to the analytical concentration of 6350 mg/m3 under the test conditions of this study. There was no evidence of immunoglobulin G (IgG) deposition in the kidneys and lungs of exposed animals. In the O'Regan and Turgeon study, the infusion of antiglomerular basement memrane into the rats did not result in linear bonding to alveolar basement membrane which suggested that the

Executive summary:

Two studies have investigated whether exposure to gasoline is associated with Goodpasture's Syndrome, a disorder of the immune system. Kuna and Uhlrich did inhalation studies on Sprague-Dawley rats and squirrel monkeys, Saimiri sciureus, and looked for evidence of immunoglobulin G (IgG) deposition in the kidneys and lungs of exposed animals, but did not find any. These investigations were continued in a study by O'Regan and Turgeon. In this work, male Sprague-Dawley rats were treated with high doses of gasoline by inhalation, tracheal intubation and intravenous injection. Infusion of antiglomerular basement membrane into the rats did not result in linear bonding to alveolar basement membranes, suggesting that the endothilial barrier remained intact.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

6 350 mg/m³

Study duration:

subchronic

Species:

rat

Effect on immunotoxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

immunotoxicity, other

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available