Acrylonitrile

Immunotoxicity

Description of key information

A sub-chronic oral study in the rat is available for acrylonitrile, which specifically investigates the potential immunotoxicity of acrylonitrile.

Key value for chemical safety assessment

Effect on immunotoxicity: via oral route

Link to relevant study records

Reference

Endpoint:

immunotoxicity: sub-chronic oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

English abstract of a Chinese literature paper

Qualifier:

no guideline followed

Principles of method if other than guideline:

The stated objective of this study was to explore the effects of acrylonitrile on T-lymphocyte subsets, expression of toll-like receptor 4 and related cytokines in rats following sub-chronic oral epxosure.

GLP compliance:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Dose / conc.:

0 mg/kg bw/day

Dose / conc.:

5 mg/kg bw/day

Dose / conc.:

10 mg/kg bw/day

Dose / conc.:

20 mg/kg bw/day

No. of animals per sex per dose:

8

Control animals:

yes

Compared with the control group, the proportions of blood CD3 and CD4 T-cells in 20 mg/kg bw/d females and the CD4:CD8 ratio in the 5, 10 and 20 mg/kg bw/d females were significantly decreased. CD8 T-cells at 20 mg/kg bw/d were significantly increased; blood CD3 T-cells in 5 mg/kg bw/d males, CD4 T-cells and CD4:CD8 ratio in 20 mg/kg bw/d males were lower than controls group. CD8 T-cells in 20 mg/kg bw/d males were significantly increased. Splenic CD4, CD8 T-lymphocyte proportions and CD4:CD8 ratio in 20 mg/kg bw/d females decreased significantly. CD8 T-cells in 20 mg/kg bw/d males were significantly increased. Splenic CD3, CD4, CD8 T-cells in 20 mg/kg bw/d males and CD4:CD8 ratio in 10 and 20 mg/kg bw/d males were also significantly decreased. CD3 T-cells in 20 mg/kg bw/d and CD8 T-cells in 10 and 20 mg/kg bw/d males were significantly increased. TLR4 mRNA expression in 5, 10 and 20 mg/kg bw/d males and 10 mg/kg bw/d females, and TLR4 protein in 5 mg/kg bw/d females and 20 mg/kg bw/d males was significantly lower than controls. The expression level of IL-1β mRNA was significantly decreased in 5, 10 and 20 mg/kg bw/d females and in males at 5 and 10 mg/kg bw/d. TNF-α mRNA expression was lower in 10 and 20 mg/kg bw/d females and in males at 5 and 10 mg/kg bw/d.

Conclusions:

The authors conclude that acrylonitrile may lead to changes in CD3, CD4 and CD8 T-lymphocyte proprotions and CD4:CD8 ratio in rat blood and spleen, and also significantly affected the expression level of TLR4 mRNA and protein together with the production of IL-1β, TNF-α. It is further postulated that these effects may cause effects on the cellular immune function.

Executive summary:

The stated objective of this study was to explore the effects of acrylonitrile on T-lymphocyte subsets, expression of toll-like receptor 4 and related cytokines in rats following sub-chronic oral exposure. Sixty-four Sprague-Dawley rats were randomly divided into 4 female groups and 4 male groups, and there were 8 rats in each group. Rats in each group were respectively given a single dose of 0, 5, 10 and 20 mg/kg bw acrylonitrile by gavage, once a day, 5 days a week, for 13 weeks. Blood and spleen T-lymphocyte subsets were detected by flow cytometry, the mRNA expression of TLR4, IL-1β and TNF-α was analysed by real-time quantitative PCR, the protein expression of TLR4 was evaluated by Western blotting. Compared with the control group, the proportions of blood CD3 and CD4 T-cells in 20 mg/kg bw/d females and the CD4:CD8 ratio in the 5, 10 and 20 mg/kg bw/d females were significantly decreased. CD8 T-cells at 20 mg/kg bw/d were significantly increased; blood CD3 T-cells in 5 mg/kg bw/d males, CD4 T-cells and CD4:CD8 ratio in 20 mg/kg bw/d males were lower than controls group. CD8 T-cells in 20 mg/kg bw/d males were significantly increased. Splenic CD4, CD8 T-lymphocyte proportions and CD4:CD8 ratio in 20 mg/kg bw/d females decreased significantly. CD8 T-cells in 20 mg/kg bw/d males were significantly increased. Splenic CD3, CD4, CD8 T-cells in 20 mg/kg bw/d males and CD4:CD8 ratio in 10 and 20 mg/kg bw/d males were also significantly decreased. CD3 T-cells in 20 mg/kg bw/d and CD8 T-cells in 10 and 20 mg/kg bw/d males were significantly increased. TLR4 mRNA expression in 5, 10 and 20 mg/kg bw/d males and 10 mg/kg bw/d females, and TLR4 protein in 5 mg/kg bw/d females and 20 mg/kg bw/d males was significantly lower than controls. The expression level of IL-1β mRNA was significantly decreased in 5, 10 and 20 mg/kg bw/d females and in males at 5 and 10 mg/kg bw/d. TNF-α mRNA expression was lower in 10 and 20 mg/kg bw/d females and in males at 5 and 10 mg/kg bw/d. The authors conclude that acrylonitrile may lead to changes in CD3, CD4 and CD8 T-lymphocyte proprotions and CD4:CD8 ratio in rat blood and spleen, and also significantly affected the expression level of TLR4 mRNA and protein together with the production of IL-1β, TNF-α. It is further postulated that these effects may cause effects on the cellular immune function.

Endpoint conclusion

Quality of whole database:

A single non-standard published study is available for this endpoint

Mode of Action Analysis / Human Relevance Framework

In a sub-chronic oral rat study, Li et al. (2014) conclude that acrylonitrile may lead to changes in CD3, CD4 and CD8 T-lymphocyte proprotions and CD4:CD8 ratio in rat blood and spleen, and also significantly affected the expression level of TLR4 mRNA and protein together with the production of IL-1β, TNF-α. It is further postulated that these effects may cause effects on the cellular immune function.

Justification for classification or non-classification

The findings in the single available study are not sufficient for classification.