Bis[[R-(R*,S*)]-β-hydroxy-α-methylphenethyl)methylammonium] sulphate

Carcinogenicity

Description of key information

Under the conditions of the test, there was no evidence of carcinogenicity for F334/N rats or B6C3F1 mice of either sex receiving 125 or 250 ppm ephedrine sulfate in diet for 2 years.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

chronic

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Since there is no evidence for a carcinogenic potential, ephedrine sulphate does not have to be classified as being carcinogenic in accordance with Directive 67/548/EEC (DSD) and EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.

Additional information

In a chronic carcinogenicity study (NTP 1986), ephidrine sulfate was administered by diet to F344/N rats and B6C3F1 mice at concentrations of 0, 125 or 250 ppm for 103 weeks (50 animals/sex/group). Doses are based on 13-week studies (the major response that occurred during the 13-week studies was compound-associated reduction in weight gain). In the 2 year study performed prior to GLP, the estimated average amount of ephedrine sulfate consumed per day was 4 mg/kg bw/day and 9 mg/kg bw/day for low dose and high dose male rats, 5 mg/kg bw/day and 11 mg/kg bw/day for female rats, 14 mg/kg bw/day and 29 mg/kg bw/day for male mice, and 12 mg/kg bw/day and 25 mg/kg bw/day for female mice. Survival of exposed female rats during the 2-year study was greater than that of the controls (control, 27/50; low dose, 39/50; high dose, 39/50) ; survival of exposed male rats, male mice, and female mice was comparable to that of controls. Throughout most of the study period, mean body weights of rats of each sex receiving diets containing the test substance were lower than those of controls (about 10%). The average daily feed consumption was 94% and 92% that of the controls for low dose and high dose males and 92% and 89% for females. Throughout most of the study period (after week 10 of the study time), mean body weights of mice of each sex receiving diets containing the test substance were lower than those of controls (at high doses up to ca. 20%). The average daily feed consumption by both dosed male mouse groups was 100% that of the controls and by low dose and high dose female mice, 97% and 94% that of the controls. At necropsy, the following tissues were examined: gross lesions, skin, mandibular lymph node, mammary gland, salivary gland, thigh muscle, sciatic nerve, sternebrae, vertebrae or femur including marrow, costochondral junction (rib), oral cavity, thymus, larynx and pharynx, trachea, lungs and bronchi, heart and aorta, thyroid gland, parathyroids, esophagus, stomach, duodenum, jejunum, tongue, gallbladder (mice only) regional lymph nodes, ileum, colon, cecum, rectum, mesenteric lymph node, liver, pancreas, spleen, kidneys, adrenal glands, seminal vesicles, prostate, testes, epididymis or ovaries, uterus, nasal cavity and nasal turbinates, brain, pituitary gland, spinal cord, eyes, and preputial or clitoral gland. Neoplasms that occurred in this study with rats were not considered to be related to administration of ephedrine sulfate. With regard to neoplasms in male mice, generally the incidences in the low and high dose groups were comparable with the incidences of the control group. Neoplasms that occurred in female mice were not considered to be related to administration of ephedrine sulfate. Thus, at the doses tested, there was no evidence of increased incidence of carcinogenesis. Under the conditions of this study, the NOAEL was >9 mg/kg bw/day (male rats), >11 mg/kg bw/day (female rats), >29 mg/kg bw/day (male mice) and >25 mg/kg bw/day (female mice) for carcinogenicity.