3-chloropropionic acid

Carcinogenicity

Description of key information

Supporting studies were available from publications which provide results with limited reliability.
Nevertheless, positive findings were reported.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity

Type of information:

calculation (if not (Q)SAR)

Remarks:

Migrated phrase: estimated by calculation

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Internationally accepted method (SAR analysis, EPA, USA) No data on GLP.

Principles of method if other than guideline:

Disinfection by-products (DBPs) are formed when disinfectants such as chlorine, chloramine, and ozone react with organic and inorganic matter in water. The observations that some DBPs are carcinogenic in animal studies have raised public concern over the possible adverse health effects of DBPs. To prioritize research efforts, an in-depth, mechanism-based structure–activity relationship analysis, supplemented by extensive literature search for genotoxicity and other data, was conducted for ranking the carcinogenic potential of DBPs that met the following criteria: a) detected in actual drinking water samples, b) have insufficient cancer bioassay data for risk assessment, and c) have structural features/alerts or short-term predictive assays indicative of carcinogenic potential. A semiquantitative concern rating scale of low, marginal, low-moderate, moderate, high-moderate, and high was used along with delineation of scientific rationale.

GLP compliance:

not specified

Histopathological findings: neoplastic:

effects observed, treatment-related

Details on results:

3-chloropropanoic acid was likely to be a weakly carcinogenic, or a carcinogenic toward a single species/target at relatively high doses.

Relevance of carcinogenic effects / potential:

3-chloropropanoic acid was likely to be a weakly carcinogenic, or a carcinogenic toward a single species/target at relatively high doses.

3-chloropropanoic acid was likely to be a weakly carcinogenic, or a carcinogenic toward a single species/target at relatively high doses.

Conclusions:

3-chloropropanoic acid was likely to be a weakly carcinogenic, or a carcinogenic toward a single species/target at relatively high doses.

Executive summary:

Disinfection by-products are formed when disinfectants such as chlorine, chloramine, and ozone react with organic and inorganic matter in water. The observations that some DBPs are carcinogenic in animal studies have raised public concern over the possible adverse health effects of DBPs. To prioritize research efforts, an in-depth, mechanism-based structure–activity relationship analysis, supplemented by extensive literature search for genotoxicity and other data, was conducted for ranking the carcinogenic potential of DBPs that met the following criteria: a) detected in actual drinking water samples, b) have insufficient cancer bioassay data for risk assessment, and c) have structural features/alerts or short-term predictive assays indicative of carcinogenic potential. A semiquantitative concern rating scale of low, marginal, low-moderate, moderate, high-moderate, and high was used along with delineation of scientific rationale.

3-chloropropanoic acid was likely to be a weakly carcinogenic, or a carcinogenic toward a single species/target at relatively high doses.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

Limited reliability

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

Taking into account the positive findings in the in vivo carcinogenicity studies, the test substance is classified as "CARCINOGEN" category 2 according to the UN GHS. The test substance is assigned to Packing Group 2 and to EU Risk-Phrase (R40).

Additional information

Following supporting studies on potential carcinogenicity of 3-chloropropionic acid were available in literature, however reliability is limited. Nevertheless, positive findings were reported:

A. 3-chloropropionic acid was investigated as an initiator of mouse skin tumors (Collburn and Boutwell, 1968). 25-30 skin tumor susceptible female mice were employed for each group. Mice in the experimental group received 0.3 mL of an acetone solution containing 120 µmoles of test substance. This application was repeated twice weekly for 3 weeks, followed 2 weeks later by twice-weekly applications of 0.5% croton oil in benzene (50 µL). Control groups received the six applications of test substance, but no croton oil. No deaths and little or no wounding occurred with test substance application. No papillomas and no carcinomas were observed in treated mice. The substance showed no activity as skin tumor initiator.

B. The observations that some disinfection by-products (DBP) are carcinogenic in animal studies have raised public concern over the possible adverse health effects. To prioritize research efforts, an in-depth, mechanism-based structure-activity relationship analysis, supplemented by extensive literature search for genotoxicity and other data, was conducted for ranking the carcinogenic potential of DBPs that met the following criteria: a) detected in actual drinking water samples, b) have insufficient cancer bioassay data for risk assessment, and c) have structural features/alerts or short-term predictive assays indicative of carcinogenic potential. A semiquantitative concern rating scale of low, marginal, low-moderate, moderate, high-moderate, and high was used along with delineation of scientific rationale. 3-chloropropanoic acid was likely to be a weakly carcinogenic, or a carcinogenic toward a single species/target at relatively high doses (Woo et al. 2002).

C. The abilities of 3-chloropropionic acid to induce lung tumors in strain A mice were investigated (Theiss et al, 1979). Groups of 20 mice (10 males and 10 females) were given 3 times weekly i.p. injections of different doses of test substance (0.14, 0.28, and 0.56 mmol/kg bw/day). When possible, 24 injections of each dose of the chemical were given, but fewer injections of the more toxic doses were administered.

Twenty-four weeks after the first injection, the mice were sacrificed, the lungs examined under a Spencer dissecting microscope and the surface adenomas were counted. A few surface nodules were examined histologically to confirm the typical morphological appearance of the adenoma. The frequency of lung tumors in each treated group was statistically compared with that in the appropriate vehicle-treated control group by both the Student t test and the X2 test. Eleven animals died during the test, one animal of the lowest dose group and ten animals of the highest dose group. Three animals (of 50) died in the control group. 3-Chloropropionic acid produced a statistically significant pulmonary adenoma response at the highest dose level. This compound is thus considered to be tumorigenic in pulmonary adenoma bioassay.

Justification for selection of carcinogenicity via oral route endpoint:
Oral study; the parenteral study provided more evidence.

Carcinogenicity: via oral route (target organ): respiratory: lung