Tungsten hexachloride

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No data is available for Tungsten hexachloride (target substance). Thus, available data from Sodium tungstate and its dihydrate (source substances) was used in a read-across approach. In a subchronic repeated dose toxicity study with focus on the male reproductive system, Sodium tungstate dihydrate was administered daily to male Wistar rats by oral gavage at dose levels of 0 and 50 mg/kg bw/day for a total of 60 days. Results in the study did not indicate that Sodium tungstate dehydrate exposure resulted in direct male reproductive toxicity in the rat. Moreover, effects on the reproductive system were assessed in a study conducted similar to the Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Study (OECD 422) (see IUCLID section 7.8.2, McInturf 2008). In this study, Sodium tungstate dihydrate was administered to 40 SD rats/sex/dose by gavage at dose levels of 0, 5, and 125 mg/kg bw/day through mating, gestation, and weaning (PND 0-20). The NOAEL for reproductive/developmental toxicity can be considered to be 125 mg/kg/day (highest dose) based on the lack of significant effects. The tests were selected to provide a screening-level assessment of a range of neurobehavioral capacities in Sodium tungstate exposed dams and their offspring. In an updated report (see IUCLID section 7.8.2, McInturf 2011) it was confirmed that daily administration of the source substance produced no overt evidence of toxicity and had no apparent effect on mating success or offspring physical development.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

125 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

comparable to guideline study

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

No data is available for Tungsten hexachloride (target substance). Thus, available data from Sodium tungstate and its dihydrate (source substances) was used in a read-across approach.

Due to a lower water solubility of Tungsten hexachloride compared to the source substances the resulting bioavailability (toxicity potential) would also be expected to be lower. Therefore, the read across to the source substances Sodium tungstate and its dihydrate is adequately protective. For justification of read-across please refer to the read-across report attached to IUCLID section 13.

In a subchronic repeated dose toxicity study with focus on the male reproductive system, Sodium tungstate dihydrate was administered daily to male Wistar rats by oral gavage at dose levels of 0 and 50 mg/kg bw/day for a total of 60 days. Results in the study did not indicate that Sodium tungstate dehydrate exposure resulted in direct male reproductive toxicity in the rat.

Moreover, effects on the reproductive system were assessed in a study conducted similar to the Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Study (OECD 422) (see IUCLID section 7.8.2, McInturf 2008). In this study, Sodium tungstate dihydrate was administered to 40 SD rats/sex/dose by gavage at dose levels of 0, 5, and 125 mg/kg bw/day through mating, gestation, and weaning (PND 0-20). The NOAEL for reproductive/developmental toxicity can be considered to be 125 mg/kg/day (highest dose) based on the lack of significant effects. The tests were selected to provide a screening-level assessment of a range of neurobehavioral capacities in Sodium tungstate exposed dams and their offspring. In an updated report (see IUCLID section 7.8.2, McInturf 2011) it was confirmed that daily administration of the source substance produced no overt evidence of toxicity and had no apparent effect on mating success or offspring physical development.

Effects on developmental toxicity

Description of key information

No data is available for Tungsten hexachloride (target substance). Thus, available data from Sodium tungstate and its dihydrate (source substances) was used in a read-across approach. Effects on the reproductive/developmental system were assessed in a study conducted similar to the Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Study (OECD 422) (see IUCLID section 7.8.2, McInturf 2008). In this study, Sodium tungstate dihydrate was administered to 40 SD rats/sex/dose by gavage at dose levels of 0, 5, and 125 mg/kg bw/day through mating, gestation, and weaning (PND 0-20). The NOAEL for reproductive/developmental toxicity can be considered to be 125 mg/kg/day (highest dose) based on the lack of significant effects. The tests were selected to provide a screening-level assessment of a range of neurobehavioral capacities in Sodium tungstate exposed dams and their offspring. In an updated report (see IUCLID section 7.8.2, McInturf 2011) it was confirmed that daily administration of the source substance produced no overt evidence of toxicity and had no apparent effect on mating success or offspring physical development.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Limit test:

no

Details on maternal toxic effects:

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS):
A statistically significant difference was found in the dams, average gestation duration was longer for the 125 mg/kg/day dose group than for the control and 5 mg/kg/day groups. Average gestational weight gain did not differ across treatments.

OTHER EFFECTS
Maternal Retrieval and Watermaze Navigation: No effects of sodium tungstate exposure at either dose were found in the dams for latency of maternal retrieval, or watermaze navigation latency or distance traveled.
Acoustic Startle/Prepulse Inhibition: For acoustic startle/prepulse inhibition, no significant main effects or interactions related to dose were found for any of the dependent measures.
Spontaneous Locomotor Activity: Exposure effects in the dams were detected for some of the measures of spontaneous locomotor activity. Specifically, dams treated with the low dose showed significantly more ambulatory time and distance travelled, as well as decreased time in stereotypies as compared to both controls and the high dose. In contrast, dams in the high dose demonstrated significantly less time resting, and more time in stereotypic movements than the vehicle controls or low dose group.

Dose descriptor:

NOAEL

Effect level:

125 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: no adverse effects observed

Abnormalities:

not specified

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects: no effects

Details on embryotoxic / teratogenic effects:
There were no differences in average number of pups born.
All pups were inspected for physical birth defects, including missing digits, however, none were found.
The high dose group demonstrated a greater number of ultrasonic distress vocalizations when separated from the dam and littermates.
Righting reflex: For righting reflex, a significant effect of sex was found (p <0.05) where males were faster (9.6±1.3 s) than females (14.5 ± 1.6 s). No significant effects related to dose were found.

Dose descriptor:

NOAEL

Effect level:

125 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: no adverse effects observed

Abnormalities:

not specified

Developmental effects observed:

not specified

Conclusions:

The tests were selected to provide a screening-level assessment of a range of neurobehavioral capacities in sodium tungstate exposed dams and their offspring. The tests evaluated reflexive responding, emotionality and spatial learning and memory. Exposure-related effects were observed both in the dams and developing pups, and for low and high dose exposures. Overall, the results of this study suggest pre- and postnatal oral exposure to sodium tungstate may produce subtle neurobehavioral effects in offspring related to motor activity and emotionality. The NOAEL for developmental toxicity was deemed to be 125 mg/kg/day.

Executive summary:

In a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Study sodium tungstate was administered to 40 SD rats/sex/dose by gavage at dose levels of 0, 5, and 125 mg/kg bw/day through mating, gestation, and weaning (PND 0-20). A statistically significant difference was found for one of the treatment groups on measures of reproductive toxicity. In the dams, average gestation duration was longer for the 125 mg/kg/day dose group than for the control and 5 mg/kg/day groups. Average gestational weight gain did not differ across treatments. In the pups, there were no differences in average number of pups born.

The NOAEL for the F1 generation was 125 mg/kg/day based on the lack of significant effects.

The Reproduction/Developmental toxicity study in the rat is classified acceptable but does not completely satisfies the guideline requirements for a developmental toxicity study (OPPTS 870.3700; OECD 414) in rodents, as no detailed examination of soft tissue or skeleton of the fetuses were conducted.

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 attached read-across report (see IUCLID section 13).

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

125 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

comparable to guideline study

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

No data is available for Tungsten hexachloride (target substance). Thus, available data from Sodium tungstate and its dihydrate (source substances) was used in a read-across approach.

Due to a lower water solubility of Tungsten hexachloride compared to the source substances the resulting bioavailability (toxicity potential) would also be expected to be lower. Therefore, the read across to the source substances Sodium tungstate and its dihydrate is adequately protective. For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Effects on the reproductive/developmental system were assessed in a study conducted similar to the Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Study (OECD 422) (see IUCLID section 7.8.2, McInturf 2008). In this study, Sodium tungstate dihydrate was administered to 40 SD rats/sex/dose by gavage at dose levels of 0, 5, and 125 mg/kg bw/day through mating, gestation, and weaning (PND 0-20). The NOAEL for reproductive/developmental toxicity can be considered to be 125 mg/kg/day (highest dose) based on the lack of significant effects. The tests were selected to provide a screening-level assessment of a range of neurobehavioral capacities in Sodium tungstate exposed dams and their offspring. In an updated report (see IUCLID section 7.8.2, McInturf 2011) it was confirmed that daily administration of the source substance produced no overt evidence of toxicity and had no apparent effect on mating success or offspring physical development.

Justification for classification or non-classification

Based on the available data from the read-across partner Sodium tungstate and its dihydrate, the target substance Tungsten hexachloride does not warrant classification for reproductive toxicity in accordance to CLP regulation 1272/2008.