National Toxicology Program

TR-305
Toxicology and Carcinogenesis Studies of Chlorinated Paraffins (C23, 43% Chlorine) (CAS No. 108171-27-3¹) in F344/N Rats andB6C3F₁ Mice (Gavage Studies)

Chemical Formula: C23H41Cl7	-	3D Structure*
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Toxicology and carcinogenesis studies of chlorinated paraffins (C23, 43%chlorine), an extreme-pressurelubricant and flame retardant, were conducted by administering the chemicalincorn oil by gavage to groups of 50 F344/N rats and 50 B6C3F₁ mice of eachsex,5 days per week for 103 weeks. Additional groups of 10 rats per sex and dosewere examined at 6 and at 12 months. Male rats received doses of 0, 1,875,or3,750 mg/kg body weight; female rats were given 0, 100, 300, or 900 mg/kg.Male and female mice received 0, 2,500, or 5,000 mg/kg. Doses selected forthe2-year studies were based on the results from 13-weekstudies in which rats of each sex received 0 to 3,750 mg/kg, and mice of eachsex, 0 to 7,500 mg/kg. No toxicity of chlorinated paraffins (C23, 43%chlorine) was observed in male rats or in male or female mice in the 13-weekstudies. A dose-relatedinflammation of the liver was observed in female rats in the 13-weekstudies and in male and female rats in the 13-weekstudies and in male and female rats at 6 and 12 months in the 2-yearstudies.

Chlorinated paraffins (C23, 43% chlorine) administration did not influencemeanbody weights of rats during the 2-yearstudies, but both male and female low dose mice gained less weight than didvehicle controls or the high dose groups. Survival of dosed and vehicle controlgroups was similar for each sex and species (male rats: vehicle control, 30/50;low dose, 32/50; high dose, 27/50; female rats: 34/50; 30/50; 33/50; 31/50;male mice: 29/50; 36/50; 28/50; female mice: 21/50; 22/50; 20/50). For femalemice, 60%-70%of the early deaths in each group were attributed to utero-ovarianinfection. The lower survival for female mice may have decreased thesensitivity of this study to detect a carcinogenic effect.

Pheochromocytomas of the adrenal gland medulla occurred with anincreasedincidence in female rats exposed to chlorinated paraffins (C23, 43% chlorine)(vehicle control, 1/50; low dose, 4/50; mid dose, 6/50; high dose, 7/50).However, adrenal gland medullary hyperplasia was not increased (6/50; 3/50;1/50; 6/50). Malignant lymphomas were increased in dosed male mice (6/50;12/50; 16/50). High dose female mice showed a marginal increase in theincidence of hepatocellular carcinomas (1/50; 1/49; 6/50) and in the incidenceof adenomas or carcinomas (combined) (4/50; 3/49; 10/50).

The primary nonneoplastic lesion associated with chlorinated paraffins (C23,43% chlorine) administration was a diffuse lymphohistiocytic inflammation inthe liver and in the pancreatic and mesenteric lymph nodes of male andfemalerats. Splenic congestion was a secondary effect. These lesions occurredearlier and at lower doses in female rats than in male rats. No significantnonneoplastic lesions were considered compound related in mice.

Chlorinated paraffins (C²³, 43% chlorine) was not mutagenic instrains TA100, TA1535, TA97, or TA98 of Salmonella typhimurium in thepresenceor absence of Aroclor 1254-inducedmale Sprague-Dawleyrat or male Syrian hamster liver S9 when assayed according to thepreincubationprotocol.

An audit of the experimental data was conducted for these 2-year studies ofchlorinated paraffins (C23, 43% chlorine). No data discrepancies were foundthat influenced the final interpretations.

Under the conditions of these 2-yeargavage studies, there was no evidence of carcinogenicity of chlorinatedparaffins (C23, 43% chlorine) for male F344/N rats given 1,875 or 3,750mg/kgper day. There was equivocal evidence of carcinogenicity ofchlorinatedparaffins (C23, 43% chlorine) for female F344/N rats as shown by anincreasedincidence of adrenal gland medullary pheochromocytomas. There wasclearevidence of carcinogenicity of chlorinated paraffins (C23, 43% chlorine)for male B6C3F₁ mice as shown by an increase in the incidence of malignantlymphomas. There was equivocal evidence of carcinogenicity ofchlorinated paraffins (C23, 43% chlorine) for female B6C3F₁ mice as shownby amarginal increase in the incidence of hepatocellular neoplasms.

¹The Chemical Abstract Service Service (CAS) number that appeared on this technical report at the time of publication (63449-39-8) reflects the generic CAS number for chlorinated paraffins. This number has been replaced in the NTP Chemtrack chemical tracking system with the more appropriate number.

Report Date: May 1986

Target Organs & Incidences from 2-year Studies

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