Cadmium telluride

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

A sub chronic toxicity and male/ female fertility study conducted in rats designed to assess the effects of cadmium telluride on male and female gametogenesis, female cyclicity, fertilization and implantation (Chapin et al., 1994). Female rats (10 per group) were dosed for 28 days (study days 0-27) by gavage to 0, 10, 30 or 100 mg/kg/d CdTe. Males (10 per group) were dosed for 24 days (study days 3-27) by gavage to 0, 10, 30 or 100 mg/kg/d. Males and females were cohabited and mated on study days 12-16.
Food consumption was variably decreased at 30 and 100 mg/kg. All dosed males gained less weight. Relative kidney weight was increased; male liver and spleen weights and all reproductive indices (fertility, sperm count, motility) were unchanged. CdTe did not alter the number of live implants, resorptions or corpora lutea in females treated before/during/after cohabiting with treated males, although body wt gain was inhibited by CdTe.
These data show that, despite effects on body wt gain, this duration of CdTe dosing had no detectable effects on male or female rat reproduction.

Link to relevant study records

Reference

Endpoint:

reproductive toxicity, other

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Short-term reproductive and developmental toxicity screen (28days). Males (group 1) are, prior to chemical exposure, cohabited with a group of females (group3) for the first 3 days of the study. The animals are separated at the end of cohabitation. The females are housed until they are dosed from gestation day 6-15. They are allowed to give birth, and rear their young until postnatal day 4. Meanwhile, the males are dosed from study day 3 until 27. These males are again mated with another group of females (group2) from study day 12 until 16. During this time, both sexes are treated with the compound.

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

no information

Route of administration:

oral: gavage

Vehicle:

other: 0.5% hemimethylcellulose

Details on exposure:

The test substance was suspended in 0.5% hemimethylcellulose and administred to adult male and female Spragley-Dawley rats daily by oral gavage.

Details on mating procedure:

- M/F ratio per cage: 1:1
- Length of cohabitation: 3 days and afterwards 5 days with respective females groups
- Proof of pregnancy: Sperm in vaginal smear or plug during cohabitation

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

-males (group 1): dosed from study day 3 until study day 27
-females (group 2): continuously exposed: day 0 until day 27
-females (group 3): gestational exposure: day 6 until day 15

Frequency of treatment:

Daily

Details on study schedule:

Males (group 1) are, prior to chemical exposure, cohabited with a group of females (group3) for the first 3 days of the study. The animals are separated at the end of cohabitation. The females are housed until they are dosed from gestation day 6-15. They are allowed to give birth, and rear their young until postnatal day 4. Meanwhile, the males are dosed from study day 3 until 27. These males are again mated with another group of females (group2) from study day 12 until 16. During this time, both sexes are treated with the compound.

Dose / conc.:

10 mg/kg bw/day

Dose / conc.:

30 mg/kg bw/day

Dose / conc.:

100 mg/kg bw/day

No. of animals per sex per dose:

10

Control animals:

yes, concurrent no treatment

Details on study design:

- Dose selection rationale:
A 28-day dose-range-finding (DRF) study was conducted to set doses for the main study. This DRF study involved no mating, just dosing to group-housed adult rats. 8 animals/ sex/dose. Doses tested were: 1000, 500, 250, 100 and 0 mg/kg/d. Hematological, clinical chemistry and body/organ weight effects were found at the lowest level (100mg/kg/d). Main study doses were set at 10,30, 100 mgCdTe/kg/d

Positive control:

None

Parental animals: Observations and examinations:

BODY WEIGHT: Yes
- Time schedule for examinations: group 1: day 3,7,11,15, 19, 23, 28; group 2: day 0,4,8,12,16,20,24,28; group 3: gestation day 0,6,10, 15 and post natal day 1, 4

FOOD CONSUMPTION :
- Food consumption for each animal determined and calculated as mean daily g food/kg body weight/day: Yes

Oestrous cyclicity (parental animals):

Number of live implants
Early/late resorptions
Total implants/ corpora lutea

Sperm parameters (parental animals):

Parameters examined in male parents:
Epididymal sperm motility and total epididymal sperm count

Litter observations:

PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
Number of pups, stillbirths, live births, postnatal mortality, weight gain

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: All surviving animals at day 28
- Maternal animals: All surviving animals after postnatal day 4
HISTOPATHOLOGY / ORGAN WEIGHTS: on liver, kidney, testis, spleen

Postmortem examinations (offspring):

No data

Statistics:

None

Reproductive indices:

None

Offspring viability indices:

None

Clinical signs:

not specified

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

males: dose-related decrease in body weight gain, with the high dose animals (30 and 100 mg/kg/day) losing weigth during the study
females (group 2): animals in the top dose (100 mg/kg bw) gained less than half the weight that controls gained over the course of the study

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

males: reduced during the first 11 days of the exposure in the high dose group (100 mg/kg bw) only
females (group 2): high dose group (100 mg/kg bw) consumed slightly less food than controls

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

males: eosinophils were reduced at the high dose group (100 mg/kg bw)

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

males: serum enzymes indicative of liver damage and serum albumin levels were slightly increased in the high dose group

Urinalysis findings:

no effects observed

Description (incidence and severity):

males: no increase in urinary cadmium or protein levels

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

males: no changes in the structure of kidneys or livers

Other effects:

not specified

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS):
group 1 (males): dose related decrease in body weight gain, with the high dose animals losing weight during the study. Food consumption is reduced during the first 11 days of exposure only in the high dose group
group 2 (females- continuously exposed): animals in the top dose group consumed slightly less food than controls and gained less than half the weight that controls gained during the course of the study
group 3 (females -gestational exposure): females dosed during fetal organogenesis with the high dose level consumed less food than controls, and animals in the middle dose group consumed less food from gestational day 8-12. There was a dose-related inhibition of weight gain that started at the lowest dose group, and animals in both middle and high dose groups gained significantly less weight during the experiment and finished lighter than controls.

REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS): no change in any fertility endpoint (number of live implants, number of dead implants, number of resorptions, number of corpora lutea

REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS): no effects on sperm parameters, fertility before and during chemical administration (group 1 males)

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS): no adverse effects seen

ORGAN WEIGHTS (PARENTAL ANIMALS): no effects on organ weights (group 1 males)

HISTOPATHOLOGY (PARENTAL ANIMALS): No changes in the structure of kidneys or livers (known target organs of cadmium toxicity) (sytemic toxicity only evaluated in males)

OTHER FINDINGS (PARENTAL ANIMALS): eosinophils were reduced at the high dose group. Serum enzymes indicative of liver damage were slightly increased in the high dose group. Serum albumin levels were increased slightly; no increase in Cd-U or in protein levels

Dose descriptor:

NOAEL

Remarks:

reproductive

Effect level:

100 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

reproductive function (oestrous cycle)

reproductive function (sperm measures)

reproductive performance

Clinical signs:

not specified

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not specified

VIABILITY (OFFSPRING): no increase in fetal loss before or after birth

BODY WEIGHT (OFFSPRING): no effects on the pups

Dose descriptor:

NOAEL

Generation:

F1

Sex:

male/female

Basis for effect level:

other: no adverse effects on birth weight, weigth gain of the pups after birth; viability: no increase in fetal loss before or after birth

Remarks on result:

other: not quantifiied

Reproductive effects observed:

not specified

none

Conclusions:

The authors conclude that despite effects on body weight gain, this duration of CdTe dosing had no detectable effects on male/female rat reproduction.
Overall the available data indicate that CdTe is not classifiable as a reproductive toxicant

Executive summary:

A Short-term reproductive and developmental toxicity screen test (28days)with 10 Sprague-Dawley rats/sex/dose was conducted. A pilot dose-range-finding study found hematology, clin chem, and body/organ weight effects at the lowest level (100 mg/kg/d); main study doses were set at 10, 30, and 100 mg CdTe/kg/d, p.o. in 0.5% methylcellulose. Food consumption was variably decreased (less than or equal to 18%) at 30 and 100 mg/kg. All dosed males gained less weight; the high dose group lost 23 gr (3.7% body wt). Relative kidney weight was increased; male liver and spleen wts and all reproductive indices (fertility, sperm #, motility) were unchanged. CdTe did not alter the number of live implants, resorptions or corpora lutea in females treated before/during/after cohabiting with treated males, although body wt gain was inhibited by CdTe (less than or equal to 50%). Another group of females was dosed GD 6-15 only, and delivered their litters; all were killed pnd4. There was a dose-related decrease in dam body wt in all CdTe groups (on pnd1, less than or equal to 15%), with no change in the number of live pups delivered, postnatal deaths or pup wt at or after birth.

These data show that, despite effects on body wt gain, this duration of CdTe dosing had no detectable effects on male or female rat reproduction.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Species:

rat

Additional information

In a combined reproductive and developmental toxicity study in rats, CdTe dosed orally up to 100 mg/kg/d had no effect on the reproductive performance of either male or female animals (Chapin et. al., 1994).

Despite effects on body weight gain, this duration of CdTe dosing had no detectable effects on male/female rat reproduction as shown by the absence of effects on microscopic structure of selected male tissues (including testis, right epididymis and left cauda), male reproductive parameters (sperm motility assessment and fertility before and during chemical administration) or female fertility endpoints (percentage pregnant, number of live and dead implants, number of corpora lutea and number of uterine implant sites at necropsy).

Overall the available data indicate that CdTe is not to be classified as a reproductive toxicant.

Effects on developmental toxicity

Description of key information

A short-term developmental toxicity screen conducted in rats dosed orally via gavage on GD 6 -15 with either 0, 10, 30 or 100 mg/kg bw/d of CdTe. There was a dose-related decrease in dam body wt in all CdTe groups (on pnd1, less than or equal to 15%), with no change in the number of live pups delivered, postnatal deaths or pup wt at or after birth (Chapin et al., 1994).  

These data show that, despite effects on body wt gain, this duration of CdTe dosing had no detectable effects on early embryo development.

 

A full justification for the waiving of a PNDT study on CdTe, based on 3 criteria according to REACH Annex IX, 8.7 Col2, is provided in IUCLID 7.8.2 Developmental Toxicity.

The conclusion for each criterion is as follows:

 

1. Low Toxicological Activity

 

From the evaluation of all available mammalian toxicity and in vitro studies (see Appendix 3 of Waiver PNDT IUCLID 7.8.2), there is no evidence of toxicity seen in any of the tests conducted with CdTe.  This fulfils the first criterion.

 

1. No Systemic Absorption Occurs via Relevant Routes of Exposure

 

In the comparative toxicokinetic study (Lourens, 2020 – Charles River Laboratories; see IUCLID 7.1 Toxicokinetics, IUCLID 7.5.2 repeated dose toxicity: oral), the results demonstrated a significant difference in bioavailability potential between a relatively soluble cadmium compound, cadmium chloride - CdCl2 (the reference substance) and the relatively insoluble cadmium compound, CdTe (test substance). CdTe exhibited no evidence of bioavailability by dietary administration for 90 days at high dose levels of 750 and 1500 ppm. No detectable and/or reliable levels of either cadmium or tellurium were detected in the target organs (liver and kidney), plasma and urine. In contrast, in the CdCl2 group, at a much lower dose level of (30 ppm), the cadmium levels increased in the kidney and liver in line with the Loeser and Lorke study (1977).

The second criterion (absence of systemic absorption via relevant routes of exposure from toxicokinetic data) is therefore met by the substance CdTe.

 

 

• No or No Significant Route of Exposure

 

The human exposure during the life cycle of CdTe was determined using the ECHA Guidance on intermediates and on information requirements and chemical safety assessment (see CSR – Occupational exposure assessment - Exposure based adaptation)[1].  As detailed in IUCLID 13.2, no significant human exposure was established for CdTe and therefore, the third criterion is fulfilled.

 

The conditions to waive the requirement for a PNDT study,  are therefore met.  This addresses the request for a PNDT study as a result of the Compliance Check by ECHA and in addition, meets the REACH Regulation “promot[ion of] the development of alternative methods for the assessment of hazards of substances”[2] to minimise unnecessary animal testing. 

 

 

[1] ECHA Guidance on intermediates, ECHA Guidance on information requirements and chemical safety assessment

[2] REGULATION (EC) No 1907/2006, Recital (1).

Link to relevant study records

Reference

Reference 1

Endpoint:

developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is of low toxicological activity (no evidence of toxicity seen in any of the tests available), it can be proven from toxicokinetic data that no systemic absorption occurs via relevant routes of exposure (e.g. plasma/blood concentrations below detection limit using a sensitive method and absence of the substance and of metabolites of the substance in urine, bile or exhaled air) and there is no or no significant human exposure

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING

See document attached under attached justification below:
- Data waiver_PNDT

Species:

rat

Reference 2

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

Short-term reproductive and developmental toxicity screen (28days). Males (group 1) are, prior to chemical exposure, cohabited with a group of females (group3) for the first 3 days of the study. The animals are separated at the end of cohabitation. The females are housed until they are dosed from gestation day 6-15. They are allowed to give birth, and rear their young until postnatal day 4. Meanwhile, the males are dosed from study day 3 until 27. These males are again mated with another group of females (group2) from study day 12 until 16. During this time, both sexes are treated with the compound.

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

no information

Route of administration:

oral: gavage

Vehicle:

other: 0.5% hemimethylcellulose

Details on exposure:

The test substance was suspended in 0.5% hemimethylcellulose and administred to adult male and female Spragley-Dawley rats daily by oral gavage.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

none

Details on mating procedure:

M/F ratio per cage: 1:1
- Length of cohabitation: 3 days and afterwards 5 days with respective females groups
- Proof of pregnancy: Sperm in vaginal smear or plug during cohabitation

Duration of treatment / exposure:

-day 6 until day 15 of gestation (females: group 3)
-continuously exposed: day 0 until day 27 (females: group 2)

Frequency of treatment:

Daily

Duration of test:

28 days

Dose / conc.:

10 mg/kg bw/day

Dose / conc.:

30 mg/kg bw/day

Dose / conc.:

100 mg/kg bw/day

No. of animals per sex per dose:

10

Control animals:

yes, concurrent no treatment

Details on study design:

Dose selection rationale:
A 28-day dose-range-finding (DRF) study was conducted to set doses for the main study. This DRF study involved no mating, just dosing to group-housed adult rats. 8 animals/ sex/dose. Doses tested were: 1000, 500, 250, 100 and 0 mg/kg/d. Hematological, clinical chemistry and body/organ weight effects were found at the lowest level (100mg/kg/d). Main study doses were set at 10,30, 100 mgCdTe/kg/d

Maternal examinations:

BODY WEIGHT: Yes
- Time schedule for examinations: group 3: gestation day 0,6,10, 15 and post natal day 1, 4, group 2: day 0,4,8,12,16,20,24,28

FOOD CONSUMPTION :
- Food consumption for each animal determined and calculated as mean daily g food/kg body weight/day: Yes

Ovaries and uterine content:

- Number of live implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: Total implants/ corpora lutea

Fetal examinations:

no

Statistics:

none

Indices:

no information

Historical control data:

no information

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

females: group 3: dose related inhibtion of weight gain that started at the lowest dose group, and animals in both middle and high dose groups gained significantly less weight during the experiment and finished lighter than controls

females (group 2): animals in the top dose (100 mg/kg bw) gained less than half the weight that controls gained over the course of the study

Number of abortions:

no effects observed

Pre- and post-implantation loss:

no effects observed

Early or late resorptions:

no effects observed

Dead fetuses:

no effects observed

Details on maternal toxic effects:

Details on maternal toxic effects:
- Mortality and time to death: no death occurred
- Body weight gain: dose-related inhibition of weight gain that started at the lowest dose group, and animals in the both middle and high dose groups gained significantly less weight
- Food consumption: the females dosed during fetal organogenesis with the high dose level consumed less food than controls, and animals in the middle dose group consumed less food from gestational day 8-12.

Dose descriptor:

NOAEL

Basis for effect level:

other: maternal toxicity

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Dose descriptor:

LOAEL

Effect level:

10 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day

Basis for effect level:

other: developmental toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
- mortality: no increase in fetal loss before or after birth
- Weight: no adverse effect on birth weight or weight gain of the pups after birth

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

reduction in number of live offspring

fetal/pup body weight changes

changes in postnatal survival

Abnormalities:

not specified

Developmental effects observed:

not specified

none

Conclusions:

Oral CdTe exposure in the pregnant rat is associated with a dose related decrease in dam body weight in all CdTe groups but no change in life pups delivered, post-natal deaths or pup weight at or after birth are observed.

Executive summary:

A Short-term reproductive and developmental toxicity screen test (28days)with 10 Sprague-Dawley rats/sex/dose was conducted. A pilot dose-range-finding study found hematology, clin chem, and body/organ weight effects at the lowest level (100 mg/kg/d); main study doses were set at 10, 30, and 100 mg CdTe/kg/d, p.o. in 0.5% methylcellulose. Food consumption was variably decreased (less than or equal to 18%) at 30 and 100 mg/kg. All dosed males gained less weight; the high dose group lost 23 gr (3.7% body wt). Relative kidney weight was increased; male liver and spleen wts and all reproductive indices (fertility, sperm #, motility) were unchanged. CdTe did not alter the number of live implants, resorptions or corpora lutea in females treated before/during/after cohabiting with treated males, although body wt gain was inhibited by CdTe (less than or equal to 50%). Another group of females was dosed GD 6-15 only, and delivered their litters; all were killed pnd4. There was a dose-related decrease in dam body wt in all CdTe groups (on pnd1, less than or equal to 15%), with no change in the number of live pups delivered, postnatal deaths or pup wt at or after birth.

These data show that, despite effects on body wt gain, this duration of CdTe dosing had no detectable effects on male or female rat reproduction or early embryo development.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Species:

rat

Additional information

In a combined reproductive and developmental toxicity study in rats,CdTe dosed orally up to 100 mg/kg/d showed no detectable effects on early embryo development (Chapin et. al., 1994). Oral CdTe exposure in the pregnant rat is associated with a dose related decrease in dam body weight in all CdTe groups but no change in life pups delivered, post-natal deaths or pup weight at or after birth are observed.

Overall the available data (Chapin et al., 1994 and Lourens (2020) indicate that CdTe is not to be classified as a developmental toxicant.

Justification for classification or non-classification

There is no experimental evidence that would justify a classification of cadmium telluride for hazardous effects for reproductive or developmental toxicity.