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Description of key information

The risk assessment of calcium carbide is driven by local effects to the lung (respiratory irritation). Thus, data on respiratory irritation is provided and complemented by information on systemic toxicity of calcium (oral route) and acetylene (inhalation route, IUCLID section 7.5.2 and 7.7).

A short-term repeated dose toxicity study with the substance as such was disregarded due to major deficiencies in methodology and documentation.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

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Endpoint:
sub-chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
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
Analytical verification of doses or concentrations:
no
Frequency of treatment:
daily ad libitum
Positive control:
No
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
effects observed, treatment-related
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
no effects observed
Details on results:
No mortality occured in all experiments.

Exp I: body wights decreased in the high dose, still within the 10% of the control group. Minor changes in some hematological and biochemical parameters, suggesting nephrotoxicity and hepatotoxicity at the high dose group; however, not accopmpanied by histological findings. Only histopathological finding relevant to treatment in the high dose group was some mild effects: localized erosion, necrosis and atrophy in the mucosa of the grandular stomach.
Exp II: Body weights significantly reduced in the 30% group. Histological examination showed nephrocalcinosis in all groups, including the control.
Exp III: nephrocalcinosis detected only in the group fed with the synthetic diet B.

Key result
Dose descriptor:
NOAEL
Effect level:
1 840 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
female
Basis for effect level:
other: overall effects; no severe toxicological findings detected.
Key result
Critical effects observed:
not specified
Conclusions:
5% calcium lactate in drinking water resulted in minor toxicological findings, such as minor changes in some hematological and biochemical parameters, and minor decreases in body weights. No severe toxicological findings were seen in the histopathological examination. The NOAEL can be set at 5%, i.e. 1840 mg/kg bw.
Executive summary:

The subchronic toxicity of calcium lactate was studied using F344 rats. In Experiment I, calcium lactate was mixed at 5, 2.5, 1.25, 0.6, and 0.3% in the drinking water and the rats were given this solution ad libitum for 13 weeks. As a result, the inhibition of body weight gain in the 5% group fell within 10% of that in the control group. Some examination values showed variations in the hematological and hematobiochemical studies, but no controversial findings were obtained in the pathohistological search. Since the highest solubility of calcium lactate is 5%, Experiments II and III were carried out by giving blended diet in order to study the toxicity at higher doses. In Experiment II, calcium lactate was mixed at concentrations of 30, 20, 10, and 5% in the B-blend powder diet and then the rats were given this diet ad libitum for 20 weeks. In Experiment III, the rats were given the CRF-1 or the B-blend powder diet ad libitum for 8 weeks. As a result, in Experiment II, nephrocalcinosis was observed in all the groups including the control group. The degree of the lesion was in reverse correlation with the administered concentrations of calcium and the lesion was seen more intensely in female rats. In Experiment III, nephrocalcinosis resulting from the administration of the B-blend diet was already observed in the 4th week. Nephrocalcinosis as observed in Experiments II and III was attributable to the small Ca/P value in the B-blend diet and not related to the calcium content per se in the diet. The NOAEL is set at 1840 mg/kg bw.

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:
short-term repeated dose toxicity: oral
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
a short-term toxicity study does not need to be conducted because a reliable sub-chronic (90 days) or chronic toxicity study is available, conducted with an appropriate species, dosage, solvent and route of administration
other:
Critical effects observed:
not specified
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
2019
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Justification for type of information:
The present study shows major deficiencies in method and documentation. First of all, the report does not state sufficient details for gavage administration, including vehicle and the form, in which calcium acetylide was applied. In case of calcium acetylide, this however is important as the substance reacts violently with water to generate gaseous acetylene and calcium hydroxide, thereby leading to a local depletion of water. The reaction is exothermic and can locally create excess heat, which can potentially lead to local burns and tissue damage. Second, the test material specifications regarding the purity of the applied calcium acetylide and the content of potential impurities, was not specified. It is mentioned in the report that calcium acetylide often contains impurities including arsenic and phosphorous, which themselves can exert toxic effects potentially covering those of the test substance.
The study conception is furthermore not compliant to the relevant OECD TG 407 guideline for a short-term repeated dose toxicity study. Several shortcomings include the use of only one sex (males), a lower number of total animals (6 instead of 10 animals per dose), and the use of two instead of three dose groups. This impairs a robust assessment of dose-dependency of effects. In addition, there was no justification for the selection of dose levels.
Furthermore, a detailed list of findings for individual animals was not reported. Significant histopathological findings were only reported in the high dose group of calcium acetylide treatment and included desquamation of the lining epithelium of the stomach, necrosis of villi and different degrees of mucosal degeneration in the small intestine. These signs indicate that local effects could be involved in the observed signs of toxicity.
Evaluation of the inherent quality of the provided data with the ECVAM ToxRTool resulted in the assignment of Klimisch category 3. Consequently, and especially in the light of the missing details on oral administration of calcium acetylide, the study design and reporting do not allow a thorough evaluation of the observed effects.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
Deviations:
yes
Remarks:
6 animals / group, 2 test groups
GLP compliance:
not specified
Remarks:
based on the published data the registrant cannot decide whether or not the study has been conducted under GLP conditions
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Route of administration:
oral: gavage
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
30 days
Frequency of treatment:
once per day
Dose / conc.:
50 mg/kg bw/day (nominal)
Dose / conc.:
100 mg/kg bw/day (nominal)
No. of animals per sex per dose:
6
Control animals:
yes, concurrent no treatment
Positive control:
no
Observations and examinations performed and frequency:
body weight examined weekly
Sacrifice and pathology:
At the end of the experiment, the animals were euthanized using standard procedure.The organs were excised, and blood was collected in EDTA tubes. Serum was used for biochemical analysis. The organosomatic index (relative organ weight) was also calculated.
Statistics:
one-way analysis of variance (ANOVA) followed by the Dunnett multiple comparison test using GraphPad Prism 7.0. p < 0.05
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
The administration of CaC2 for 30 days produced mild changes in body weight and food and water consumption compared with the normal rats.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
The administration of CaC2 for 30 days produced mild changes in body weight and food and water consumption compared with the normal rats.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Description (incidence and severity):
Group Hb, g/dL RBC, Platelet Total WBC Neutrophil Lymphocyte Eosinophil
millions/cu count, count,
mm 105/cu mm cells/cu
mm
Normal 14.36 ± 0.68 5.56 ± 0.22 2.86 ± 0.39 4116.66 ± 354.49 31.16 ± 5.91 65.83 ± 5.63 3 ± 0.63

CaC2, 100 14.2 ± 0.57 5.55 ± 0.21 3.03 ± 0.32 5900 ± 25.33 ± 71.83 ± 2.83 ± 0.75
mg/kg 732.12 04. Mrz Mrz 48
CaC2, 50 13.98 ± 5.48 ± 0.11 3.88 ± 0.48 4708.33 ± 26.83 ± 69.83 ± 3.333 ±
mg/kg 0.23 420.02 Mai 19 Mai 34 01. Mrz
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Organosomatic Normal CaC2, 100 mg/kg CaC2, 50 mg/kg
index

Brain 0.651 ± 0.083 0.518 ± 0.098 0.609 ± 0.057
Lung 0.630 ± 0.149 0.559 ± 0.096 0.525 ± 0.159
Liver 2.576 ± 0.151 2.738 ± 0.197 2.542 ± 0.160
Pancreas 0.151 ± 0.026 0.127 ± 0.022 0.141 ± 0.020
Spleen 0.275 ± 0.058 0.285 ± 0.038 0.311 ± 0.065
Kidney 0.584 ± 0.060 0.636 ± 0.060 0.574 ± 0.071
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Histological observations of various organs like liver, kidney, lungs, and small intestine (duodenum, jejunum,
and ileum) showed toxic changes at high doses of CaC2. CaC2-treated liver displayed dilated
central vein, congested sinusoids, and microvesicular fatty change with vacuolated large hepatocytes. Macroscopically,
there was a pale hard mass on the posterior surface of the liver.
Histopathological analysis of lungs showed dense lymphocyte infiltration at high doses of
CaC2. Stomach histology showed desquamating lining epithelium, increase in mucous gland in the
lamina propria by the treatment of CaC2 at the high doses. Histological observations of small intestine
showed necrosis of villi in all treated groups, by using an intestinal mucosal lesion
scoring system (0–4). Regular morphology was represented as 0, subepithelial congestion with slight cellular
desquamation at the villi tips as score 1, mucosal congestion with loss of less than half of the villi as score 2, loss
of more than half of the villi as score 3, and submucosal degeneration as score 4. According to
intestinal mucosal lesion scoring, extremely significant injuries were observed in all the treated groups except
low-dose (50 mg/kg) CaC2-treated animals. Neither morphological nor structural changes were observed in
various organs like heart, brain, pancreas, spleen, etc.
Key result
Dose descriptor:
NOEL
Effect level:
50 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
histopathology: non-neoplastic
Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
100 mg/kg bw/day (nominal)
System:
gastrointestinal tract
Organ:
not specified
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
yes
Conclusions:
Industrial-grade CaC2 showed at lower doses mild to moderate toxicity to the internal organs of rats and a decline in hemoglobin level. The elevated platelet, WBC count, and lymphocyte infiltration in the tissues indicate inflammatory responses. The study revealed that CaC2 are toxic to organs and might weaken the immune system.
However, the study was disregarded due to major deficiencies in study design and documentation.
Executive summary:

In a subacute toxicity study performed according to OECD 407, CaC2 was administered to 6 male Wistar rats/dose by oral gavage at dose levels of 50 and 100 mg/kg bw/day for 30 days. At subacute doses, RBC and hemoglobin levels were found to be declined (p< 0.01), whereas total WBC and platelet counts, especially lymphocytes, were elevated remarkably (p < 0.01). Total protein, albumin, and urea were also found to be increased (p< 0.01). Histopathological observations support the toxicity in rats at higher doses (100 mg/kg bw/day) of CaC2. The study revealed that CaC2 cause toxic effects on the internal organs of rats. The subsequent inflammatory response might have weakened the immune system. Based on the results of this study, the NOAEL is considered to be 50 mg/kg bw/day.

The study was disregarded due to major deficiencies in method and documentation. First of all, the report does not state sufficient details for gavage administration, including vehicle and the form, in which calcium acetylide was applied. In case of calcium acetylide, this however is important as the substance reacts violently with water to generate gaseous acetylene and calcium hydroxide, thereby leading to a local depletion of water. The reaction is exothermic and can locally create excess heat, which can potentially lead to local burns and tissue damage. Second, the test material specifications regarding the purity of the applied calcium acetylide and the content of potential impurities, was not specified. It is mentioned in the report that calcium acetylide often contains impurities including arsenic and phosphorous, which themselves can exert toxic effects potentially covering those of the test substance.

The study conception is furthermore not compliant to the relevant OECD TG 407 guideline for a short-term repeated dose toxicity study. Several shortcomings include the use of only one sex (males), a lower number of total animals (6 instead of 10 animals per dose), and the use of two instead of three dose groups. This impairs a robust assessment of dose-dependency of effects. In addition, there was no justification for the selection of dose levels.

Furthermore, a detailed list of findings for individual animals was not reported. Significant histopathological findings were only reported in the high dose group of calcium acetylide treatment and included desquamation of the lining epithelium of the stomach, necrosis of villi and different degrees of mucosal degeneration in the small intestine. These signs indicate that local effects could be involved in the observed signs of toxicity.

Consequently, and especially in the light of the missing details on oral administration of calcium acetylide, the study design and reporting do not allow a thorough evaluation of the observed effects concerning the involvement of systemic or local non-specific mode of actions of the substance.

Based on the deficiencies described, evaluation of the inherent quality of the provided data with the ECVAM ToxRTool resulted in the assignment of Klimisch category 3 and thus the study was not regarded suitable for the assessment of repeated dose toxicity of the test substance calcium acetylide.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
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
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Key result
Dose descriptor:
NOAEC
Effect level:
250 000 ppm
Based on:
test mat.
Sex:
not specified
Basis for effect level:
gross pathology
Remarks on result:
not determinable
Remarks:
no NOAEC identified
Key result
Critical effects observed:
not specified

In treated animals that survived to termination, no evidence of cellular injury to the parenchymatous cells of the heart, lungs, liver, kidneys, or spleen was reported. However, capillary hyperemia of the liver, kidneys and spleen was observed in some rats exposed to 25%. This effect was observed until at least the second day after the last exposure to the gas but was not evident in animals killed later (up to 5 days after the last exposure). Since capillary hyperemia was not observed in rats exposed to higher concentrations of acetylene, it does not appear to be test-material related.

Conclusions:
Repeated exposure of rats to a concentration of 25% acetylene (1h/day for up to 93 days) did not cause any organ toxicity.
Executive summary:

In a non-guideline subchronic inhalation toxicity study, acetylene was administered to 2 -47 rats/sex/concentration by whole body exposure at concentrations of 0 and 25,000 ppm daily for 1 hour for up to 93 days.

In treated animals that survived to termination, no evidence of cellular injury to the parenchymatous cells of the heart, lungs, liver, kidneys, or spleen was reported. However, capillary hyperemia of the liver, kidneys and spleen was observed in some rats exposed to 25%. This effect was observed until at least the second day after the last exposure to the gas but was not evident in animals killed later (up to 5 days after the last exposure). Since capillary hyperemia was not observed in rats exposed to higher concentrations of acetylene, it does not appear to be test-material related.

Based on the results of this study, the NOAEC is considered to be 25,000 ppm.

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:
short-term repeated dose toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
a short-term toxicity study does not need to be conducted because a reliable sub-chronic (90 days) or chronic toxicity study is available, conducted with an appropriate species, dosage, solvent and route of administration
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
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
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Key result
Dose descriptor:
NOAEC
Effect level:
250 000 ppm
Based on:
test mat.
Sex:
not specified
Basis for effect level:
gross pathology
Remarks on result:
not determinable
Remarks:
no NOAEC identified
Key result
Critical effects observed:
not specified

In treated animals that survived to termination, no evidence of cellular injury to the parenchymatous cells of the heart, lungs, liver, kidneys, or spleen was reported. However, capillary hyperemia of the liver, kidneys and spleen was observed in some rats exposed to 25%. This effect was observed until at least the second day after the last exposure to the gas but was not evident in animals killed later (up to 5 days after the last exposure). Since capillary hyperemia was not observed in rats exposed to higher concentrations of acetylene, it does not appear to be test-material related.

Conclusions:
Repeated exposure of rats to a concentration of 25% acetylene (1h/day for up to 93 days) did not cause any organ toxicity.
Executive summary:

In a non-guideline subchronic inhalation toxicity study, acetylene was administered to 2 -47 rats/sex/concentration by whole body exposure at concentrations of 0 and 25,000 ppm daily for 1 hour for up to 93 days.

In treated animals that survived to termination, no evidence of cellular injury to the parenchymatous cells of the heart, lungs, liver, kidneys, or spleen was reported. However, capillary hyperemia of the liver, kidneys and spleen was observed in some rats exposed to 25%. This effect was observed until at least the second day after the last exposure to the gas but was not evident in animals killed later (up to 5 days after the last exposure). Since capillary hyperemia was not observed in rats exposed to higher concentrations of acetylene, it does not appear to be test-material related.

Based on the results of this study, the NOAEC is considered to be 25,000 ppm.

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:
short-term repeated dose toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
a short-term toxicity study does not need to be conducted because a reliable sub-chronic (90 days) or chronic toxicity study is available, conducted with an appropriate species, dosage, solvent and route of administration
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEC
5 mg/m³
Study duration:
subacute
Species:
other: human volunteers and workers
Quality of whole database:
For Study see section 7.10.3
Respiratory irritation of calcium oxide/hydroxide has been assessed in several studies in volunteers and in occupational settings. The information is considered relevant for the risk assessment of calcium carbide.

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
sub-chronic toxicity: dermal
Data waiving:
other justification
Justification for data waiving:
other: