Calcium acetylide

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

three-generation reproductive toxicity

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

Clinical signs:

not examined

Dermal irritation (if dermal study):

not examined

Mortality:

not specified

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

effects observed, treatment-related

Description (incidence and severity):

At the highest level of calcium (2.0g/100g diet), there was a significant decrease in the total number weaned (p<0001) and the total weight weaned (p<0.001).
Although the differences in the numbers born at the different CaCO, levels were not statistically significant, it may be noted that there was some decrease at the two higher levels (1.0 and 2.0g/100g diet)
A few animals suffered from vaginal prolapse and failed to produce any litters after the first, which should be attributed to genetic causes.

Experiment 1:
Weight of heart, liver, spleen, and kidneys were not affected in mothers.
Higest level of Ca showed significant decrease in total number weened.
Few animals had vaginal prolapse and failed to produce litters after the first, may be attritubed to genetics.

Experiment 2:
Addition of Fe, P, or higher level of CaCO3 has no significant effects on the number of young born in first or second litter.
The number and weight weaned were affected by the number of failures to rear first litters (6 failures in higher Ca groups, 1 failure in lower Ca group). Mice that failed rearing first litters all succeeded in rearing some young in subsequent litters, therefore the number of total deaths did not differ greatly.
Organ weight - higher levels of CaCO3 increased absolute and relative heart weight and decreased percentage of heart dry matter.

Key result

Dose descriptor:

LOAEL

Effect level:

20 000 mg/kg diet

Based on:

test mat.

Sex:

female

Basis for effect level:

reproductive performance

Critical effects observed:

not specified

Clinical signs:

not examined

Dermal irritation (if dermal study):

not examined

Mortality / viability:

mortality observed, treatment-related

Description (incidence and severity):

First litters: At the highest level of calcium (2.0g/100g diet), there was a significant increase in both the number and proportion of deaths (p<0.01)
Second and subsequent litters showed greater viability as indicated in a lower proportion of deaths. The average number of deaths on diets with the highest level of CaCO3, was significantly higher than on diets with lower levels of CaCO3 (P=0.01) and the highest proportion of deaths also occurred with the highest CaCO3 level (p<0.001).

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Considering the weight per litter weaned, thus eliminating the effect of litters dying before weaning, a gradation is apparent in the results, the highest weight being found at the low dose level (0.5g/100g diet), with a marked falling off at the two highest dose levels (1.0g and 2.0g/100g diet). When calculating the mean weight per litter weaned, this effect was most pronounced at the highest dose level (0/0.5/1.0/2.0g/100g diet: 40.5g/53.3g/39.4g/23.3g)

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Sexual maturation:

not examined

Anogenital distance (AGD):

not examined

Nipple retention in male pups:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

As the investigation of organ weights was not begun from the start of the experiment, the results are incomplete and are therefore not recorded in detail, but sufficient evidence is available to show that there was a significant effect of CaCO3 in increasing the heart weights of the weanlings. The heart weights of the mothers were not significantly affected. Although the effect of CaCO3 on the thymus weights of the weanlings was not found to be statistically significant when all the results were analysed, there was a tendency for thymus weights to decrease as heart weights increase with increasing levels of CaCO3.
Analysis of the weights (mg/100g body-weight) of liver, spleen and kidneys of the young mice and their mothers did not reveal any significant effects of calcium or other dietary factors on these organs.
In experiment 2, the percentage of dry matter in the heart was significantly lowered by the higher level of Ca (P<0.001). Thymus weights of second litters were significantly affected both by the Ca additions, but in the opposite direction from the heart weights. Thus the absolute weight of the thymus and its weight relative to body-weight were both diminished by the higher level of Ca (P<0.001).

Gross pathological findings:

not examined

Histopathological findings:

not examined

Other effects:

not examined

Behaviour (functional findings):

not examined

Developmental immunotoxicity:

not examined

Experiment 1:
Highest level of Ca had significant decrease in total weight weened and total number weaned and significantly increased number and proportion of deaths. There were non-significant differences in the numbers born at different CaCO3 levels, but some decrease at the two higher levels. Best results were from 0.5g/100g CaCO3.
Second and subsequent litters showed greater viability. Results showed a significant decrease in total weight of weaned animals and total number of weaned animals in the highest level CaCO3. Average number of deaths and highest proportion of deaths occurred at the highest level of CaCO3. Critical periods in rearing young mice were the first and third weeks of life.
Organ weights - frequent occurence of pale speckled livers, enlarged hearts, and small thymus glands, which were more pronounced in groups wiht higher levels of CaCO3. CaCO3 had a significant effect on increasing heart weights of weanlings, but no significant effects on thymus weight. There were no significant effects on weights of liver, spleen, and kidneys in young mice.

Experiment 2:
Total weight weaned was lower in higher CaCO3 group due to litter failures, for groups without litter failures, weigh weaned was similar. Adding Fe and P inproved diet and decreased the effects of higher levels of CaCO3. Weaning weights per litter increased in subsequent groups, amplified by addition of Fe and P, except one group, which showed no difference.
Organ weights - higher levels of CaCO3 were seen to increase absolute heart weight and relative heart weight in weanlings. Fe supplementation significantly decreased relative and absolute heart weight in higher and lower CaCO3 groups. P had no significant effect on relative or absolute heart weight. Percentage of heart dry matter was significantly decreased by higher CaCO3 levels and significantly increased by Fe; P had no significant effect. A significant correlation exists between heart enlargement and degree of anaemia. Thymus weight of second litters were significantly decreased by higher levels of CaCO3 and increased by Fe; P had no significant effect.

Key result

Dose descriptor:

LOAEL

Generation:

F1

Effect level:

20 000 mg/kg diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

mortality

organ weights and organ / body weight ratios

Critical effects observed:

not specified

Reproductive effects observed:

not specified

In a breeding test on mice, using the method of continuous monogamous mating, three levels of calcium carbonate were added to different diets. On all the diets the highest addition of calcium carbonate, which gave a Ca intake of 1.1% and a Ca:P ratio of approximately 2,3, there was a significantly lowered number and total weight of young weaned and an increased number and proportion of deaths. There was also some decrease in the number of births. Both absolutely and relatively to body-weight the heart weights of the weanlings were significantly increased by Ca and decreased by Fe, whereas thymus weights were decreased by Ca and increased by Fe. The high Ca level also caused a significant increase in the absolute and relative heart weights of the mothers. Although the percentage of dry matter in the hearts of the weanlings was significantly lowered by the higher level of Ca, there was a marked increase in the absolute weight of heart dry matter at this level, indicating the presence of a cardiac hypertrophy. A highly significant relationship was found between heart weight and blood haemoglobin in the weanling mice, an increase in heart weight accompanying a decrease in Hb. The relationship between log heart weight, expressed in mg food/g body-weight, and log Hb was linear.

Conclusions:

In a breeding test on mice, the highest dose tested (1400 mg Calcium/kg bw/d) significantly lowered the number and total weight of young weaned and increased the number and proportion of deaths. There was also some decrease in the number of births. The study design does not fulfill requirements of an OECD 416 study. Results cannot be used to derive a NOAEL.

Executive summary:

In a multi-generation reproduction study, CaCO3 was administered to 4-8 Swiss mice/sex/dose in diet at dose levels of 0, 5000, 10 000, and 20 000 mg/kg food and 250, 700, 1400 mg Calcium/kg bw/d. The first litter and subsequent litters up to 2 litters was observed. The highest dose tested significantly lowered the number and total weight of young weaned and increased the number and proportion of deaths. There was also a decrease in the number of births. Results cannot be used to derive a NOAEL. This study does not fulfill the requirement for a multi-generational reproductive study (OECD 416) in rodents due to lack of experimental information on animals and test substance, and lack of observational, reproductive, and terminal data; as well as lack of reported data on the previously listed parameters.

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.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

In aqueous solution, calcium carbide rapidly decomposes into calcium hydroxide and acetylene. Calcium hydroxide dissociates into calcium and hydroxyl ions. As hydroxyl ions are readily buffered in biological tissue, only calcium ions and gaseous acetylene need to be assessed for potential effects on reproduction. Acetylene is released as a gas. It has a long history of use as general anaesthetic and is considered to be of very low toxicity (disregarding the "narcotic" effects). Calcium is the most abundant mineral in the human body and part of the normal diet (approx 700 mg/day; SCF 2003). Due to the fact that risk assessment of calcium carbide is driven by local effects (respiratory irritation) in the range of 1-5 mg/m³ (6.3-31,5 mg calcium/person/day), calcium is not expected to have adverse effects at these concentrations. This conclusion is supported by a multi-generation study with calcium carbonate (Richards 1952), and several studies according to or similar to OECD 414 using calcium oxide/carbonate (Shackelford 1993, 1994; Bailey 1974; Lai 1984; Corbellini 1991). This conclusion is also in line with the assessment of the tolerable daily intake of 2.500 mg calcium/day (TDI) [EFSA 2012, see IUCLID section 7.12].

The second decomposition product, acetylene, has been used for over 100 years as an anesthetic and as an industrial chemical, and few complications of using this gas have surfaced (US EPA, HPV review 2006). In addition, exposure to acetylene would be very low at an occupational exposure level of 1-5 mg/m³ calcium carbide. Assuming an air volume of 10 m³ inhaled during an 8-hour workday, exposure to acetylene would be in the range of 0.05-0.3 mg/kg/d [1 mg/m³ calcium carbide equals 0.4 mg acetylene/m³; 0.4 mg/m³ × 10 m³/8h shift = 4 mg/person/d = 0.05 mg/kg bw/d (70 kg worker)]. The concentration of acetylene that is systemically available would be even smaller, since a fraction of acetylene would be exhaled after decomposition of calcium carbide in contact with the mucous membrane in the lung. Thus, conducting a two-generation study with calcium carbide is considered to be scientifically unjustified.

Justification for selection of Effect on fertility via oral route:
The risk assessment of calcium carbide is driven by local effects to the lung (respiratory irritation). At concentration relevant for respiratory irritation (1 -5 mg/m3), possible systemic toxicity of the decomposition products of calcium carbide, calcium hydroxide and acetylene, can be neglected.

Effects on developmental toxicity

Link to relevant study records

Reference

Reference 1

Endpoint:

developmental toxicity

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

Species:

rat

Strain:

other: CD/VAF Plus

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
Clinical: alopecia, exudate around the eyes, exudate around the nose, bent teeth, lesion, lump in the left flank or leg and mammary lump. However, no dose response association. Three females died during the study (non-treatment related). The treatment showed some variations on the food consumption; however, not all differences were statistically significant. No body weight gain effects were detected. Relative organ weights to body weights of the treated groups were not significantly different from the controls. Implantations, resorptions and litter sizes were comparable to controls and did not appear influenced by the high calcium consumption.

Key result

Dose descriptor:

NOAEL

Effect level:

227.5 other: mg calcium/day

Based on:

act. ingr.

Basis for effect level:

other: developmental toxicity

Key result

Dose descriptor:

NOAEL

Effect level:

288.75 other: mg calcium/day

Based on:

act. ingr.

Basis for effect level:

other: developmental toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No adverse effects were detected on the foetuses. Foetal body weights and lengths were within the normal control values. No effect related to the treatment was seen on the number of litters.

Key result

Dose descriptor:

NOAEL

Effect level:

1.25 other: % in diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects observed

Abnormalities:

not specified

Developmental effects observed:

not specified

More details on the results are presented in the attached pdf document.

Conclusions:

There was no adverse developmental/teratogenic effects related to high dietary calcium intake, i.e. 1.25% of the daily diet, of animals, 6 weeks before mating, throughout mating and 20 days during pregnancy. Additionally, such levels did not affect the reproductive performance parameters examined in this study.

Executive summary:

In the present study the potential effects of high dietary calcium on pregnancy and development of the foetus were studied in rats. Female Charles River CD/VAF Plus rats were fed a diet containing various levels of calcium, i.e. 0.5 (control), 0.75, 1.00, or 1.25% as calcium carbonate, 6 weeks before mating, throughout mating and 20 days during gestation. On gestation day 20, the animals were killed, and caesarian sections were performed. The uterine contents were examined and the foetuses were evaluated for soft tissue and skeletal changes. The treatment showed some variations on the food consumption of the females. Nonetheless, not all differences were statistically significant, and they could not be attributed to the treatment. No body weight gain effects were detected. Relative organ weights to body weights of the treated groups were not significantly different from the controls. Implantations, resorptions and litter sizes were comparable to controls and did not appear influenced by the high calcium consumption. It can be concluded that calcium up to 1.25% in the diet, is not foetotoxic or teratogenic.

 

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.

Reference 2

Endpoint:

developmental toxicity

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

Species:

other: mice and rats

Strain:

other: CD-1 and Wistar

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
Mice:
There were no effects on nidation or maternal survival.

Rats:
There were no effects on nidation or maternal survival.

Key result

Dose descriptor:

NOAEL

Effect level:

440 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: no adverse effects observed for maternal toxicity

Key result

Dose descriptor:

NOAEL

Effect level:

680 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: no adverse effects observed for maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Mice:
There were no effects on fetal survival. Soft or skeletal tissues of test groups did not differ from sham-treated controls.

Rats:
There were no effects on fetal survival. Soft or skeletal tissues of test groups did not differ from sham-treated controls.

Key result

Dose descriptor:

NOAEL

Effect level:

440 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects observed for developmental toxicity

Key result

Dose descriptor:

NOAEL

Effect level:

680 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects observed for developmental toxicity

Abnormalities:

not specified

Developmental effects observed:

not specified

No effects indicative of maternal (death, weight) or developmental toxicity (number of corpora lutea, implantation and resorption sites, and live and dead fetuses; fetal weights; skeletal and visceral abnormalities) were seen in Wistar rats (n=19-21/group) and CD-1 mice (n=17-21/group) given daily oral (gavage) doses of CaO, administered as a water suspension, of 6.8-680 and 4.4-440 mg/kg bw, respectively, during gestational days 6-15 (Bai74). [The committee notes that due to the way the substance was administered not calcium oxide per se but calcium hydroxide was tested].

Conclusions:

No effects indicative of maternal (death, weight) or developmental toxicity (number of corpora lutea, implantation and resorption sites, and live and dead fetuses; fetal weights; skeletal and visceral abnormalities) were seen in Wistar rats (n=19-21/group) and CD-1 mice (n=17-21/group) given daily oral (gavage) doses of CaO, administered as a water suspension, of 6.8-680 and 4.4-440 mg/kg bw, respectively, during gestational days 6-15

Executive summary:

In a developmental toxicity study performed similar to OECD TG 414, calcium oxide was administered to female Wistar rats (n=19-21/group) and CD-1 mice (n=17-21/group) by oral gavage at dose levels of 4.4-440 mg/kg (mice) and 6.8 - 680 mg/kg (rats) respectively, from days 6 through 15 of gestation. No effects indicative of maternal (death, weight) or developmental toxicity (number of corpora lutea, implantation and resorption sites, and live and dead fetuses; fetal weights; skeletal and visceral abnormalities) were seen.

Therefore, both the maternal and developmental NOAEL is considered to be 440 mg/kg (mice) and 680 mg/kg (rats), respectively.

The developmental toxicity study in the rat is classified acceptable and satisfies the guideline requirement for a developmental toxicity study (OPPTS 870.3700; OECD 414) in rodents.

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.

Reference 3

Endpoint:

developmental toxicity

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

Species:

other: ewe

Strain:

other: Rambouillet-Columbia

Details on maternal toxic effects:

Maternal toxic effects:no effects

Key result

Remarks on result:

not measured/tested

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
The thyroid glands of the fetuses from animals of the high calcium group contained significantly more C cells than these from animals of the normal calcium goup. The treatment seemed to affect the width of the articular cartilage of the epiphysis. The fetuses of mothers fed with the high calcium diet had retarded cartilage differentiation in the proximal humeral epihysis and metaphysis and transverse trabeculation in the epiphysis. According to the authors these are typical characteristics of osteochondrosis.

Dose descriptor:

LOAEL

Effect level:

3 800 other: mg calcium/day

Based on:

act. ingr.

Basis for effect level:

other: fetotoxicity

Abnormalities:

not specified

Developmental effects observed:

not specified

Conclusions:

High levels of dietary calcium (1.52% calcium in diet, i.e. 3800 mg/day) in pregnant sheep induced abnormal bone formation in the fetuses (osteochondrosis).

Executive summary:

In a non-guideline developmental toxicity study, calcium carbonate was administered to ewes ad libitum (up to a maximum of 2.5 kg/day) in diet at levels resulting in 0.59% and 1.52% calcium on a dry matter basis from gestational day 50 to days 133 to 135.

A maternal NOAEL/LOAEL could not be determined due to a lack of data on maternal endpoints.

The thyroid glands of the fetuses from animals of the high calcium group contained significantly more C cells than these from animals of the normal calcium goup. The treatment seemed to affect the width of the articular cartilage of the epiphysis. The fetuses of mothers fed with the high calcium diet had retarded cartilage differentiation in the proximal humeral epihysis and metaphysis and transverse trabeculation in the epiphysis. According to the authors these are typical characteristics of osteochondrosis. Based on a these results, the developmental LOAEL is considered to be 1.0% calcium (corresponding to 10800 mg/kg diet). The developmental NOAEL is 1.52% calcium (corresponding to 3800 mg Ca/day).

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.

 

Reference 4

Endpoint:

developmental toxicity

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

Species:

rat

Strain:

Sprague-Dawley

Details on maternal toxic effects:

Maternal toxic effects:yes. Remark: effects on food consumption and body weights

Details on maternal toxic effects:
Pregnant animals fed with the high content calcium diet had a significantly decreased food consumption, that had an obvious effect on the body weight gain.

Key result

Dose descriptor:

LOAEL

Effect level:

144 other: mg/day

Based on:

act. ingr.

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Details on embryotoxic / teratogenic effects:
Significantly less growth of products of conception was seen in rats fed with the high calcium diet than in rats on normal calcium or calcium-free diet, probably due to decreased food consumption. Nonetheless, the fetuses body weights, although slightly decreased, did not show any statistically signifcant change when compared to controls. The viable litter sizes of the three groups were identical.

Key result

Dose descriptor:

LOAEL

Effect level:

144 other: mg/kg/day

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

changes in litter size and weights

Abnormalities:

not specified

Developmental effects observed:

not specified

Table 1: Intake of diet containing various levels of calcium

	Total diet intake
Diet	Pregnant (g diet/21 days)	Non Pregnant (g diet/21 days)
Normal calcium	324 ± 37	278 ± 15
Calcium-free	353 ± 22	311 ± 19
High calcium	280 ± 30	287 ± 14

As mentioned above the calcium content was 15, 580, 1080 mg/100 g diet (calcium free, normal calcium, high calcium).

Assuming an average diet intake of 13.3 g/ day, for the high content calcium group, this would lead us in approximately 144 mg calcium/rat per day.

Table 2: Reproductive performence on rats

Diet	No of rats	Weight of products of conception (uterus, placenta, foetuses and amniotic fluid) (g)	Fetal weight (g)	Litter size
Normal calcium	5	73 ± 8	4.6 ± 0.5	11 ± 2
Calcium-free	5	76 ± 5	5.2 ± 0.2	11 ± 1
High calcium	7	58 ± 9	4.2 ± 0.4	10 ± 2

Conclusions:

The study suggests that 144 mg calcium/day 1.0% calcium (corresponding to 10800 mg/kg diet) during pregnancy, does affect the food intake and body weight of the pregnant rats. Consequently, the weight of the products of conception were significantly reduced. No effects were seen on the litter sizes and foetal weights.

Executive summary:

In a non-guideline developmental toxicity study, calcium carbonate was administered to female Sprague-Dawley rats in diet at levels resulting in 0.01%, 0.6% and 1.0% calcium (150, 5800 and 10800 mg/kg diet) from gestational day 1 to day 16 and day 22.

In maternal animals fed with high-dose levels, reduced food consumption and body weight gain was observed. The maternal LOAEL is therefore 1.0% calcium (corresponding to 10800 mg/kg diet). The maternal NOAEL is 0.6% calcium (corresponding to 5800 mg/kg diet).

Based on a decreased weight in products of conception at the high calcium dose, the developmental LOAEL is considered to be 1.0% calcium (corresponding to 10800 mg/kg diet). The developmental NOAEL is 0.6% calcium (corresponding to 5800 mg/kg diet).

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.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

In aqueous solution, calcium carbide rapidly decomposes into calcium hydroxide and acetylene. Calcium hydroxide dissociates into calcium and hydroxyl ions. As hydroxyl ions are readily buffered in biological tissue, only calcium ions and gaseous acetylene need to be assessed for potential effects on reproduction. Acetylene is released as a gas. It has a long history of use as general anaesthetic and is considered to be of very low toxicity (not counting the "narcotic" effects). Calcium is the most abundant mineral in the human body and part of the normal diet (approx 700 mg/day; SCF 2003). Due to the fact that risk assessment of calcium carbide is driven by local effects (respiratory irritation) in the range of 1-5 mg/m3 (6.3 - 31,5 mg calcium/person/day), calcium is not expected to have adverse effects at these concentrations. This conclusion is supported by a multi-generation study with calcium carbonate (Richards 1952), and several studies according to or similar to OECD 414 using calcium oxide/carbonate (Bailey 1974, Shackelford 1993/1994, Lai 1984, and Corbellini 1991). It is also in line with the assessment of the tolerable daily intake of 2.500 mg calcium/day (TDI) [EFSA 2012, see 7.12].

The second decomposition product, acetylene, has been used for over 100 years as an anesthetic and as an industrial chemical, and few complications of using this gas have surfaced (US EPA, HPV review 2006). In addition, exposure to acetylene would be very low at an occupational exposure level of 1-5 mg/m³ calcium carbide. Assuming an air volume of 10 m³ inhaled during an 8-hour workday, exposure to acetylene would be in the range of 0.05-0.3 mg/kg/d [1 mg/m³ calcium carbide equals 0.4 mg acetylene/m³; 0.4 mg/m³ × 10 m³/8h shift = 4 mg/person/d = 0.05 mg/kg bw/d (70 kg worker)]. The concentration of acetylene that is systemically available would be even smaller, since a fraction of acetylene would be exhaled after decomposition of calcium carbide in contact with the mucous membrane in the lung. Thus, conducting a developmental toxicity study with calcium carbide is considered to be scientifically unjustified.

Justification for selection of Effect on developmental toxicity: via oral route:
The risk assessment of calcium carbide is driven by local effects to the lung (respiratory irritation). At concentration relevant for respiratory irritation (1 -5 mg/m3), possible systemic toxicity of the decomposition products of calcium carbide, calcium hydroxide and acetylene, can be neglected.

Justification for classification or non-classification

The risk assessment of calcium carbide is driven by local effects to the lung (respiratory irritation). At concentration relevant for respiratory irritation (1 -5 mg/m3), possible systemic toxicity of the decomposition products of calcium carbide, calcium hydroxide and acetylene, can be neglected.