1,2-dichloropropane

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

62 mg/kg bw/day

Study duration:

chronic

Species:

rat

Additional information

The oral repeat dose toxicity of 1,2-dichloropropane has been investigated extensively by NTP (1986) in a series of GLP-compliant studies using male and female F344 rats and B6C3F1 mice. Key aspects of the design of these studies, along with the main findings, are summarized in Table 3.1.5. The results indicate that the liver is a target organ after gavage administration, with a chronic NOAEL of 125 mg/kg bw/day in female rats (males unaffected) and a chronic LOAEL of 125 mg/kg bw/day in male mice (females unaffected). Acanthosis of the stomach (indicative of persistent local irritation) was noted in mice (rats unaffected) with a chronic NOEL of 125 mg/kg bw/d in males and a chronic LOEL of 125 mg/kg bw/d in females. Body weight was decreased 14-24% in rats (chronic NOELmales = 62 mg/kg bw/d, chronic NOEL females = 125 mg/kg bw/d) whereas mice were unaffected (chronic NOEL = 250 mg/kg bw/d, both sexes). The overall NOAEL values following chronic administration of PDC were 62 and 125 m/kg bw/d for male and female rats respectively. No chronic NOAEL was derived for mice of either sex; the LOAEL was 125 m/kg bw/d.

The neurological consequences of repeated oral exposure to 1,2-dichloropropane have been investigated in F344 rats (n = 15/sex/group) given 0 (corn oil), 20, 65 or 200 mg/kg bw/day for 13 weeks by gavage (Johnson and Gorzinski, 1988). The study followed U.S. E.P.A. guidelines and was conducted to the standards of GLP. Prior to treatment, and at monthly intervals during the study, all animals were assessed for a number of endpoints including functional observational battery, hindlimb grip strength, and motor activity. After a 13-week treatment, 4 rats/sex/dose were randomly selected for terminal examination (including histopathological examination of brain, spinal cord and nerve) while the remainder were retained (no further treatment) for a 9 week recovery period. Transient clinical signs (lacrimation, blinking, and decreased spontaneous motor activity) were reported on days 3-4 of treatment, and body weight was slightly decreased at week 13 in both sexes. There were no effects attributable to 1,2-dichloropropane in the functional observational battery, grip strength, or motor activity. Results from the gross and microscopic examination of the brain and nervous system revealed no treatment-related lesions.

Overall, apart from a minor effect on body weight (NOAELmales= 20 mg/kg bw/day; NOAELfemales 65 mg/kg bw/day), no adverse structural or functional neurological consequences were apparent in rats following 13 weeks gavage administration of 1,2-dichloropropane at doses up to 200 mg/kg bw/day.

 

In conclusion, results from repeat dose studies indicate that theliveris a target organ in rodents with a chronic oral NOAEL of 62 -125 mg/kg bw/d in rats and a chronic LOAEL of 125 mg/kg bw/d in mice (no NOAEL established). There were no adverse systemic organ effects in rats and mice following sub-chronic exposure to 150 ppm 1,2-dichloropropane (NOAEL), whereas red blood cell parameters (regenerative anemia) were altered in rabbits with a LOAEL of 150 ppm in males and a NOAEL of 150 ppm in females. Body weight was slightly but statistically significantly decreased in rats only (NOAEL 15 ppm) in these sub-chronic inhalation studies, with site-of contact (irritative) changes present in stomach (mouse, NOAEL/LOAEL 125 mg/kg bw/d after oral gavage, dependent on sex) and nasal tissue (rat, NOAEL 15 ppm after inhalation; rabbits, NOAEL 500 ppm).

 

NOAEL: 62 mg/kg bw is the lowest value among all available studies

Justification for classification or non-classification

Results of repeated toxicity studies did not lead to the classification of 1,2-dichloropropane for long term effects.