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Administrative data

Description of key information

In an oral toxicity study with zinc lactate the LD50 was estimated to be 1190 mg/kg bw. In studies performed with soluble zinc salts as suitable read-across substances no adverse effects were observed that would warrant classification for acute dermal and inhalation toxicity.

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
Study period:
1996-10-02 to 1996-12-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Date of receipt: 1996-08-12
- Name of the test substance: Puramex Zn (zinc lactate)
- General appearance: fine white powder
- Storage conditions: ambient temperature
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Germany
- Age at study initiation: 5-6 weeks old upon arrival
- Weight at study initiation: not specified
- Fasting period before study: prior to dosing, the animals were fasted overnight
- Housing: five animals per cage (stainless steel cages, fitted with wire-screen floor and front)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 to 23 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50-85
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw
Doses:
500 and 2000 mg/kg bw
No. of animals per sex per dose:
2000 mg/kg bw: 5 males; 5 females
500 mg/kg bw: 5 males, 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: All visible reactions to treatment were recorded including severity, onset and duration. Observations were made within 1 hour and within 4 hours after dosing, and subsequently at least once daily throughout an observation period of 14 days.
- Frequency of weighing: The body weight of each animal was recorded immediately before dosing on day 0 and of the surviving animals on day 3, 7 and 14 of the study.
- Termination of the study: At the end ot the observation period on day 14 of the study, all surviving animals were killed with carbon dioxide and examined for external changes. The abdomen and the thorax of each animal was opened and examined for
gross pathological changes. The animals found dead were also examined for gross pathological changes.
Statistics:
None
Preliminary study:
A screening was carried out with two males treated with a dose level of 2000 mg kg body weight to check for mortality. Since both animals survived it was decided to continue the study with that dose level.
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
> 500 - < 2 000 mg/kg bw
Mortality:
The first two males treated with the 2000 mg/kg bw dose level survived treatment, whereas the other three males and five females were found dead within 3 days after dosing. All five males and five females treated with the 500 mg/kg dose level survived.
Clinical signs:
Sluggishness, blepharospasm, piloerection, soiled fur and diarrhoea were generally observed during the first day after dosing.
Body weight:
All animals gained weight during the 14-day test period.
Gross pathology:
Macroscopic examination of the animals at the end of the observation period did not reveal treatment-related gross alterations.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In conclusion, the oral LD50 of Puramex Zn is considered to be between 500 and 2000 mg/kg bw; most likely value 1190 mg/kg bw (linear interpolation).
Executive summary:

In an acute oral toxicity study in accordance with OECD 401 the oral LD50 is considered to be between 500 and 2000 mg/kg bw; most likely value 1190 mg/kg bw (linear interpolation).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 190 mg/kg bw
Quality of whole database:
Guideline study

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Zinc lactate fully dissociates into Zn2+ ions and lactate in aqueous solutions and/or under physiological conditions. The toxicological effects of zinc lactate can be understood in terms of the toxicological effect of lactic acid and Zn2+ ions. The read across partner zinc chloride also dissociates into Zn2+ ions and the respective counter ion in aqueous media. Thus, the source substance is suitable to be used in a read-across approach.
Reason / purpose:
read-across source
Preliminary study:
Not applicable
Sex:
female
Dose descriptor:
LC50
Effect level:
2 000 mg/m³ air (analytical)
Exp. duration:
10 min
Mortality:
Two animals died at 940 and 1220 mg/m³ while all animals died at highest dose of 1950 mg/m³. For details see ‘table 1’ .
Clinical signs:
other: Respiratory distress including dyspnoea, decreased locomotor activity, laboured breathing, rhonci and rales observed.
Body weight:
Not reported
Gross pathology:
Entire surface of lungs showed discolouration (dark red), varying degrees of congestion, patchy discolouration, oedema and interstitial emphysema
Other findings:
- Histopathology: Atelectasis, hyperaemia and haemorrhages and oedema observed
- Potential target organs: Lungs

Table 1: Acute inhalation toxicity of test material in rats

 Concentration (mg Zn/m³)*

 Mortality after exposure during 10 min (number of deaths/exposed)
 600  0/3
 940  2/3
 1220  2/3
 1950  3/3

* The molar ratio of Zn:ZnCl2 is 1:2.1

Interpretation of results:
study cannot be used for classification
Conclusions:
The acute inhalation LC50 of the test material was calculated to be 2000 mg ZnCl2/m³ in rats after a exposure of 10 minutes.
Executive summary:

A study was conducted in Sprague-Dawley female rats to determine pulmonary injury after acute inhalation exposure to the test material. Animals were exposed to the test material at a concentration of 600, 940, 1220 and 1950 mg Zn/m³ (molar ratio of Zn:ZnCl2 is 1:2.1) for 10 min. Animals showed respiratory distress. Clinical examination of lung showed discolouration (dark red), varying degrees of congestion, patchy discolouration, oedema and interstitial emphysema, atelectasis, hyperaemia and haemorrhages. Based on the above results, the acute inhalation LC50 of zinc was calculated to be 954 mg Zn2+/m³. This information is used in a read-across approach for the assessment of the target substance. Considering the molar weight of zinc lactate of 243.52 g/mol, and the molar weight of zinc (65.38 g/mol), the acute inhalation LC50 of zinc lactate is estimated at 3551 mg/m³.

Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Zinc lactate fully dissociates into Zn2+ ions and lactate in aqueous solutions and/or under physiological conditions. The toxicological effects of zinc lactate can be understood in terms of the toxicological effect of lactic acid and Zn2+ ions. Thus, the source substance is suitable to be used in a read-across approach.
Reason / purpose:
read-across source
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 7.94 mg/L air
Exp. duration:
4 h
Mortality:
1 female died.
Clinical signs:
other: Animals were observed during exposure for signs of toxicity. Rapid breathing and eye tearing was observed in the treated group, while in the sham control group, respiration was calm and steady during exposure. One and three hours after exposure, the treat
Body weight:
Individual body weights for animals on test are given in Tables 4 and 5. At the beginning of the study, mean body weicihts for individual groups were within 20 % of the overall mean for each sex. All groups of male rats gained weight within the first week after exposure in comparison to pre-exposure weights (3 % for sham-exposed, 2< for SY-83, respectively). Female rats in the sham group gained weight during the first week after exposure (less than 1 %). Female rats in the treated group lost weight during the first week after exposure (7 %). After 14 days, all surviving animals had gained weight in comparison to pre-exposure weights (14 % for males, 7 % for females). No significant differences were observed in body weight between treated and control groups.
Gross pathology:
All surviving animals were necropsied at the termination of the study. The aninal that died during the study was necropsied immediately. Necropsy results are shown in Table 6. No gross lesions were observed at necropsy.
Interpretation of results:
practically nontoxic
Conclusions:
Under the conditions of the test, the LC50 of SY-83 is greater than 7.94 mg/L.
Executive summary:

SY-83 was tested for lts acute inhalation toxicity. Male and female F344 rats were exposed to a concentration of approxinately 7.94 mg/L for 4 hours. Rapid breathing and eye tearing were observed during exposure. At one and three hours after exposure, all animals (including the sham controls) had a hunched posture, ruffled and ungroomed fur, brown stained fur and red-stained fur surrounding the eyes (tearing). By 24 hours, female treated rats had ruffled and stained coats. All other animals appeared normal at 24 hours and for the remainder of the 14 day observation period. Several treated female rats continued to have ruffled fur up to 4 days after exposure. One female rat from the treated group died on day 9. All other animals survived until the end of the study. Based on these results, the LC50 of SY-83 is greater than 7.94 mg/L.

This information is used in a read-across approach for the assessment of the target substance.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
3 551 mg/m³
Quality of whole database:
Read-across from lactic acid (non-toxic) and zinc chloride in a weight-of-evidence approach. The LC50 hence is a hypothetical value, not relevant for hazard assessment since zinc lactate neither exhibits a significant vapour pressure nor a significant potential for inhalation based on the particle size (see IUCLID sections 4.5 and 4.6).

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Used in EU risk assessment report for zinc sulphate, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Type of coverage:
semiocclusive
Vehicle:
not specified
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Details on study design:
observation period of 15 days
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
none
Clinical signs:
Clinical signs of toxicity consisted of erythema (grade 1 and 2, of maximum grade 4), scales and/or scabs (scale 1 and 2, of maximum scale 3) in the treated skin area between observation days 2-8.
Body weight:
no effects
Gross pathology:
no effects
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In conclusion, the dermal LD50 is considered to be greater than 2000 mg/kg bw. Zinc sulphate is not harmful nor toxic via the dermal route.
Executive summary:

In this study zinc sulphate heptahydrate was administered to the skin of five Wistar rats of each sex at 2000 mg/kg bw for 24 hours. Animals were observed for 15 days. Clinical signs of toxicity consisted of erythema (grade 1 and 2, of maximum grade 4), scales and/or scabs (scale 1 and 2, of maximum scale 3) in the treated skin area between observation days 2-8.

Zinc sulphate is not harmful or toxic via the dermal route.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
according to
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
Young adult, New Zealand White albino rabbits were obtained from Langshaw Farms, Route l, Box 256, Augusta, MI 49012. The albino rabbit is the species preferred in the EPA/OPP Guidelines for acute dermal toxicifey testing.
Animals were housed individually in stainless steel, wire-bottomed cages that conformed to the size standards specified in DHEW Publication (NIH) 78.23. The cages on each rack were numbered in a Standard manner and a list of random numbers was generated by computer program* for the number of animals of each sex received. Upon receipt, each animal was removed from the shipping container and housed in the appropriate randomly selected cage. Each animal was then assigned a sequential animal number unique within ToxiGenics and identified with an ear tag bearing this animal number. The sequential animal number was listed on a cage card that was affixed to the front of the animal's cage.
The animals were quarantined for approximately 3 weeks after receipt. During the quarantine period, Veterinary Sciences personnel observed the animals at least once each day for mortality, morbidity, and abnormal signs. Animals were examined during quarantine and only those considered to be in good health were used in this study.
The quarantine and study room (252) was cleaned daily and the cages were cleaned and sanitized as specified in ToxiGenics1 Standard Operating Procedures. Urine and feces feil through the wire mesh floor onto animal caging board. The cage boards were changed at least 3 times a week.
The animal room was well ventilated and air-conditioned, and the temperature and humidity were monitored daily in this room during the quarantine and study periods. The temperature ranged from 68 to 70°F and the relative humidity varied from 47 to 68 percent with the following exception: a relative humidity value of 72 percent was recorded on one day during quarantine. The animal room was lighted from approximately 6:00 a.m. to 6:00 p.m. (12-hour light/12-hour dark cycle) using automatic timers. The test article applications were completed at 1:45 p.m. on October 19, 1983.
Purina Certified Rabbit Chow 5322 was fed to the animals ad libitum during the quarantine and study periods. Filtered tap water was provided ad libitum through an automatic watering system and was analyzed periodically as specified in ToxiGenics1 Standard Operating Procedures.
Type of coverage:
occlusive
Vehicle:
other: applied neat
Details on dermal exposure:
The dorsal trunk (approximately 10% of the body surface area) of each animal was clipped free of hair with Oster electric clippers equipped with a number 40 (surgical) blade. The areas were reclipped as needed during the study for evaluation of dermal reactions.
On the day of dosing (day 0), body weights were recorded and doses were calculated. Approximately 24 hours after the initial clipping, the prepared area of each animal was abraded. The
Ibngitudinal epidermal abrasions were spaced 2 to 3 cm. apart and were sufficiently deep to penetrate the stratum corneum but not the dermis. After abrading, a measured volume of the test arti- cle was introduced under an impervious binder, consisting of a
plastic wrap and adhesive tape secured around the trunk of each manually restrained animal, and gently spread over the applica-
tion site. After test article application, the trunk of each animal was wrapped with additional adhesive tape and masking tape.
After a 24-hour exposure period, each binder was removed, and the test site of each animal was wiped (not washed) with gauze sponges moistened with water to remove remaining test article
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Hourly on day 0, twice daily for all other days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None
Clinical signs:
No abnormal clinical signs were observed during the study.
Body weight:
Body weight gains were observed for all animals during the study. Four males and 4 females gained weight on days 7 and 14. One male and one female.lost either 50 or 60 grams of weight from day 0 to day 7, and gained weight from day 7 to day 14.

Severe erythema and severe edema were observed for all animals after test article removal on day 1. Erythema decreased in severity (to well defined or very slight) for 2 males on day 14 and for one female on day 12. Edema decreased in severity (to moderate, slight, or very slight) for all males and 3 females as early as day 2. No erythema was observed on day 14, and no edema was observed on days 12 to 14 for one female. Also, no edema was observed on day 14 for one male. Other dermal reactions observed at test sites included:

- Blanching: all animals on day l and as late as days 2, 3, or 4 for 6 animals.

- Necrosis (brown-green discoloration): all animals on days l and 2, as late as days 3, 5, or 6 for 3 males, and to day 11 for 4 females.

- Eschar formation: all animals on days 2 to 11, and for 7 animals to day 14. Eschar was present along the abrasion lines only of one female on days 7 to 11.

- Eschar peeled off: one female on day 12, and 2 males on day 14.

- Atonia: all males and 3 females from days 3 or 4 to days 11 or 14.

- Desquamation: all animals from days 10 or 11 to day 14.

- Fissures: one male and 4 females as early as day 5 and as late as day 14.

- Denuded areas along abrasion lines: one female on day 14. No other dermal reactions were observed during the study. Brown, crusted, and raised discolorations of the treated skin were observed during necropsy of 3 males and 3 females. Multiple depressions in the treated skin were observed during necropsy of one of the same males, of 2 other males, and of one other female. A dark red focus was also observed on the lung of one male. No other abnormalities were observed during necropsy of all males and 4 females, and no abnormalities were observed during necropsy of one female.

Interpretation of results:
other: Irritating but otherwise practically non-toxic
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
In conclusion, in an acute dermal toxicity study the test item SY-83 is not systemically toxic up to 2000 mg/kg bw, but It is irritating to the skin.
Executive summary:

The test article, SY-83, was evaluated for acute dermal toxicity at a dose level of 2000 mg/kg bw. The test article was applied to the skin (clipped free of hair and abraded) of 5 males and 5 females for 24 hours of exposure. This study was designed to comply with the procedures described in the EPA/OPP Guidelines, 1982. All animals survived the 14-day duration of the study and gained body weight. No abnormal clinical signs were observed during the study. Severe erythema and severe edema were observed at the test sites of all animals after removal on day 1. Based on the results the dermal LD50 is considered to be greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Lactic acid is a ubiquitous and essential biological molecule. It is, as expected, practically non-toxic via all routes of exposure. Effects observed for zinc lactate can be considered as zinc effects. An oral LD50 is available for zinc lactate, the inhalative LC50 and the dermal LD50 were derived from suitable read-across partners.

Justification for classification or non-classification

Based on available data, zinc lactate warrants classification for acute oral toxicity (H302, Acute Tox.4). No classification is warranted for the dermal route based on available data from suitable read-across substances. Furthermore, no classification is warranted for the inhalation route, due to the insignificant vapour pressure and and the relatively large particle size. Therefore, the adverse effects observed in an inhalation toxicity study on zinc chloride (in a read-across approach) can be ignored for classification and labelling.