Copper di-D-gluconate

Endpoint summary

Description of key information

DL50 (Oral): 1709 mg/kg bw; OECD 401

DL50 (Dermal): 2130 mg/kg bw; QSAR prediction

CL50 (inhalation): in accordance with column 2 of REACH Annex VIII, the study does not need to be conducted since exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or dorplets of an inhalable size.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Specific details on test material used for the study:

The test substance was dissolved in tap water and administered in a single dose using a stomach cannula

Species:

rat

Strain:

Wistar

Remarks:

SPF-quality, randomly bred

Sex:

not specified

Details on test animals or test system and environmental conditions:

Fourty young adult rats of the Wistar strain (SPF-quality, randomly bred) were obtained from the Broekman Institute, Someren, The Netherlands. Date of arrival at the animal house: 21-8-1984 (Dose range finding investigation) and 11-9-1984 and 18-9-1984 (Main study).
From that date on, the animals were individually housed in Macrolon cages. They had free access to tap water and standard laboratory animal diet (RMH-B, pellet diameter 10 mm), which was obtained from Hope Farms, Woerden, The Netherlands. Four days before the start of the main study the animals were randomly distributed into 3 groups with approximately equal distribution of weights. At the start of the study the body weights of the males ranged from 263 to 351 g and those of the females from 174 to 202 g. The animal room temperature was maintained at 20 +-3°C and the relative humidity at 50 - 80 per cent. The artificial light sequence was 12 hours light, 12 hours dark. Feed was withheld overnight before dosing till 4 hours after administration of the test substance.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Based on the sponsor's acute toxicity data on related metal gluconates and literature data on copper salts a pilot study was performed in order to determine a dose range. Groups of one female and one male rat received a single oral dose of the test substance in tap water: 320, 560, 1000, 1800 and 3200 mg/kg body weight.
The dosage volume amounted to 10 ml/kg body weight. Both high dose animals (3200 mg/kg) and one female adminstered 1800 mg/kg died within approximately 24 hours of dosing.
The animals of the other treatment groups revealed no symptomsof systemic toxicity during the 7-day observation period.

Doses:

The following doses have been administered: 1800, 2400, 3200 mg/kg bw. The dosage volume amounted to 10 ml/kg bw.

No. of animals per sex per dose:

Groups of 5 male and 5 female

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 709 mg/kg bw

Remarks on result:

other: The LD50 value was calculated according to the 'maximum likelihood' method of Finney (reference 3).

Mortality:

All animals of the high dose group died within 24 hours of dosing. Eight out of ten animals of the medium dose group and five out of ten animals of the low dose group were found dead within 48 hours of administration of the test substance.

Clinical signs:

other: Most animals showed apathetic behaviour and reduced locomotive activity during a 4-hour period after dos ing. These symptoms did no longer appear in the surviving animals from day 4 of the observation period.

Gross pathology:

Examination of the stomach from animals found dead revealed local haemorrhages (petechiae) and necrosis in the fundus. Moreover, the entire intestinal tract of these animals was congested. All surviving animals showed no treatment rel ated gross al terations during autopsy at the end of the 14-day observation period.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The calculated LD50 value for males and females together amounted to 1709 mg/kg body weight. Substance is classified as a Acute tox (Oral) 4.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 709 mg/kg bw

Quality of whole database:

The study is a GLP compliant and has Klimisch score 1.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Guideline:

other: REACH guidance on QSAR R6

Specific details on test material used for the study:

SMILE: OCC{P-}(O)C{P-}(O)C{P+}(O)C{P-}(O)C(=O)O{-}.[Cu]{+}

Key result

Dose descriptor:

LD50

Effect level:

2 130 mg/kg bw

Interpretation of results:

GHS criteria not met

Conclusions:

DL50= 2130 mg/kg. Substance does not classify as Acute Toxic Dermal in any category.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 130 mg/kg bw

Quality of whole database:

Toxicity of the target chemical (2.13E+03 mg/kg) is predicted by QSAR "Modelo QSAR 180404 DL50 Dermica Gluconato".The target chemical FALLS within applicability domain of the prediction. Reliability 2.

Justification for classification or non-classification

The oral LD50 was between 300 and 2000 mg/kg bw. Therefore, the substance is classified as Acute Tox. Cat. 4 (Oral)

The dermal LD50 was 2130 mg/kg bw. Therefore, the substance is not classified as Acute Tox (Dermal).