Calcium acetylide

Carcinogenicity

Description of key information

A study of workers at calcium carbide plant (Kjuus, 1986);

a long-term toxicity/carcinogenicity study of calcium lactate in F344 rats (Maekawa, 1991); and an inhalation study addressing carcinogenicity of dichloroacetylene (acetylene as control) (Reichert, 1984).

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

As calcium carbide instantly hydrolyses to Ca(OH)2 and C2H2 upon contact with water/moisture the assessment is based on the degradation products. For details please refer to the read across report in section 13.

Reason / purpose for cross-reference:

read-across source

Control animals:

yes, concurrent no treatment

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

no effects observed

Details on results:

Result (carcinogenicity): negative

Key result

Dose descriptor:

LOAEC

Effect level:

50 000 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: body weight, adrenocortical hyperplasia in males

Remarks on result:

other: Effect type: toxicity

Key result

Dose descriptor:

NOAEC

Effect level:

25 000 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: toxicity

Key result

Dose descriptor:

NOAEC

Effect level:

50 000 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: carcinogenicity

Conclusions:

It was concluded that calcium lactate had neither toxic nor carcinogenic activity in F344 rats when it was given continuously in the drinking-water for 2 yr.

Executive summary:

In a carcinogenicity study performed similar to OECD TG 453, Calcium lactate (>97% purity) was administered ad libitum to 50 F344 rats/sex/dose in drinking-water at levels of 0, 2.5 or 5% for two years. Compared with the controls, a 13% decrease in body weight gain was observed in male and female rats of the high-dose group. In females, mortality rate was slightly higher in the 5% group than those in the other groups.

Besides, no clear toxic lesion was specifically caused by long-term administration of Calcium lactate.

Based on these results, the LOAEL is considered to be 5% Calcium lactate, based on the reduction in body weight gain. The NOAEL is therefore 2.5% Calcium lactate, since no adverse effects were observed at this dose level.

No significant dose-related increase in the incidences of tumours in any organ or tissue was found. The results indicate that calcium lactate had neither toxic nor carcinogenic activity in F344 rats. Dosing is considered adequate based on the 13% reduction in body weight gain observed in the high-dose group.

This carcinogenicity study is acceptable as it was performed similar to OECD TG 453.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Carcinogenicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

As calcium carbide instantly hydrolyses to Ca(OH)2 and C2H2 upon contact with water/moisture the assessment is based on the degradation products. For details please refer to the read across report in section 13.

Reason / purpose for cross-reference:

read-across source

Details on results:

Acetylene was used as negative control in comparison to dichloroacetylene (DCA).

Key result

Dose descriptor:

NOAEC

Effect level:

21.2 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: toxicity

Conclusions:

21.2 mg/m3 (20 ppm) acetylene was used as negative control in a carcinogenicity study of dichloroacetylene.

Executive summary:

In a carcinogenicity study performed similar to OECD TG 451, acetylene in air was administered to groups of 30 Wistar rats and NMRI mice/sex at a dose level of 21.2 mg/m3 (20 ppm) acetylene for 6 hours per day, 1 -2 times weekly over a period of 18 months.

Acetylene was used as negative control in a carcinogenicity study of dichloroacetylene.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Calcium carbide is not considered to be mutagenic, and available information on the substance and its decomposition products does not indicate a direct link between exposure to calcium carbide and incidence of cancer. Therefore it is considered that classification for carcinogenicity is not justified.

Additional information

In aqueous solution, calcium carbide rapidly decomposes into calcium hydroxide and acetylene (see endpoint summary on hydrolysis of CaC2). Local effects are related to calcium hydroxide, which liberates OH- ions, affecting the skin and the mucous membranes. Systemic effects would be related to calcium ions. Calcium is the most abundant mineral in the human body and part of the normal diet (approx 700 mg/day; SCF 2003). Thus, calcium is not expected to have carcinogenic potential. Acetylene is released as a gas. It has a long history of use as a general anaesthetic and is considered to be of very low toxicity (disregarding the "narcotic" effects).

A study of workers at a single calcium carbide plant showed a decrease in stomach cancer and a significant excess of colonic cancer (standardised incidence ratio, SIR = 2.09) and prostatic cancer (SIR = 1.56). In view of the confounding factors, the lack of compositional and exposure information, and the lack of any mechanisms, it is not considered that this study is evidence for carcinogenicity. IARC have reviewed these data in consideration of possible carcinogenicity of PAHs and found that they are not classifiable as to their carcinogenicity to humans (group 3). Maekawa (1991) concluded that calcium (in form of calcium lactate) had neither toxic nor carcinogenic activity in F344 rats when it was given daily at concentrations up to 5 % in drinking water for 2 years. Reichert (1984) used acetylene (21.2 mg/m³) as negative control in a carcinogenicity study in rats and mice.

Justification for selection of carcinogenicity via oral route endpoint:
Carcinogenicity was assessed in a weight of evidence approach taking into account hazard data on calcium and acetylene.

Justification for selection of carcinogenicity via inhalation route endpoint:
Data from a study of workers at a single calcium carbide plant showed a decrease in stomach cancer and a significant excess of colonic and prostatic cancer (see IUCLID 7.10.2). In view of the confounding factors, the lack of compositional and exposure information, and the lack of any mechanisms, it is not considered that this study is evidence for carcinogenicity. IARC have reviewed these data in consideration of possible carcinogenicity of PAHs and found that they are not classifiable as to their carcinogenicity to humans (group 3). Consequently, carcinogenicity was assessed in a weight of evidence approach taking into account hazard data on calcium compounds and acetylene.